Thermal ablation compared to stereotactic body radiation therapy for hepatocellular carcinoma: A multicenter retrospective comparative study.

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.

Clinical Data Prediction Model to Identify Patients With Early-Stage Pancreatic Cancer.

PURPOSE: Pancreatic cancer is an aggressive malignancy with patients often experiencing nonspecific symptoms before diagnosis. This study evaluates a machine learning approach to help identify patients with early-stage pancreatic cancer from clinical data within electronic health records (EHRs). MATERIALS AND METHODS: From the Optum deidentified EHR data set, we identified early-stage (n = 3,322) and late-stage (n = 25,908) pancreatic cancer cases over 40 years of age diagnosed between 2009 and 2017. Patients with early-stage pancreatic cancer were matched to noncancer controls (1:16 match). We constructed a prediction model using eXtreme Gradient Boosting (XGBoost) to identify early-stage patients on the basis of 18,220 features within the EHR including diagnoses, procedures, information within clinical notes, and medications. Model accuracy was assessed with sensitivity, specificity, positive predictive value, and the area under the curve. RESULTS: The final predictive model included 582 predictive features from the EHR, including 248 (42.5%) physician note elements, 146 (25.0%) procedure codes, 91 (15.6%) diagnosis codes, 89 (15.3%) medications, and 9 (1.5%) demographic features. The final model area under the curve was 0.84. Choosing a model cut point with a sensitivity of 60% and specificity of 90% would enable early detection of 58% late-stage patients with a median of 24 months before their actual diagnosis. CONCLUSION: Prediction models using EHR data show promise in the early detection of pancreatic cancer. Although widespread use of this approach on an unselected population would produce high rates of false-positive tests, this technique may be rapidly impactful if deployed among high-risk patients or paired with other imaging or biomarker screening tools.

Impact of Radiation on Cardiovascular Outcomes in Older Resectable Esophageal Cancer Patients With Medicare.

OBJECTIVES: Preoperative radiotherapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiotherapy and different radiation techniques on cardiovascular morbidity among a cohort of esophageal cancer patients. MATERIALS AND METHODS: We identified 1125 patients aged 65 and older diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation from the Surveillance Epidemiology and End Results (SEER)-Medicare database. We used Medicare claims to identify severe perioperative and late cardiovascular events. Multivariable logistic regression and Fine-Gray models were used to determine the effect of presurgery treatment on the risk of perioperative and late cardiovascular disease. RESULTS: Preoperative chemotherapy or chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared with surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a late cardiovascular event compared with patients treated with surgery alone (subdistribution hazard ratio [SDHR]: 1.36; P=0.035). There was no significant increase in late cardiovascular events among patients treated with preoperative chemotherapy (SDHR: 1.18; P=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy had a 68% decreased risk of having a late cardiovascular event compared with patients receiving conventional radiation (SDHR: 0.32; P=0.007). CONCLUSIONS: This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as intensity modulated radiotherapy.

Phase I Trial of Stereotactic Body Radiation Therapy Dose Escalation in Pancreatic Cancer.

PURPOSE: Stereotactic body radiation therapy (SBRT) has demonstrated encouraging local tumor control rates in the treatment of pancreatic cancer, yet we lack prospective clinical trials evaluating dose-escalation strategies among patients treated with 5-fraction SBRT. This phase 1 dose-escalation trial was conducted to determine the maximum tolerated dose of SBRT in patients with pancreatic cancer. METHODS AND MATERIALS: Thirty patients with pancreatic cancer were enrolled and treated with 40, 45, or 50 Gy SBRT in 5 fractions with doses determined using a time-to-event continual reassessment method trial design. Systemic therapy was permitted before and after SBRT, but not mandated by the study protocol. Toxicity was the primary study endpoint, and any grade ≥3 acute or late toxicity potentially attributable to SBRT was considered a dose-limiting toxicity. Secondary endpoints included local progression, distant progression, and overall survival. RESULTS: The median follow up from SBRT was 8.9 months (range, 1.7-62.6 months). Nineteen patients (63%) had locally advanced disease, 3 patients (10%) had metastatic disease, and 8 patients (27%) had medically unresectable disease. Three patients (10%) received 40 Gy, 16 patients (53%) received 45 Gy, and 11 patients (37%) received 50 Gy. Seven patients (23%) experienced grade ≤2 acute toxicity, and 2 patients (6.7%) experienced grade 4 to 5 late toxicity, both of which occurred in the 45 Gy group. Median survival time was 17.1 months from the time of diagnosis and 9.8 months from SBRT. The 1-year cumulative incidence of local progression was 14.2% (95% confidence interval, 4.2%-30%). CONCLUSIONS: This dose-escalation trial evaluated high-dose SBRT delivered in 5 fractions, and overall demonstrated favorable local control and survival, but was associated with nontrivial rates of severe late gastrointestinal toxicity potentially attributable to radiation. Further prospective studies are needed to define the safety and efficacy of high-dose SBRT in patients with pancreatic cancer.

Association Between African American Race and Clinical Outcomes in Men Treated for Low-Risk Prostate Cancer With Active Surveillance.

Importance: There is concern that African American men with low-risk prostate cancer may harbor more aggressive disease than non-Hispanic White men. Therefore, it is unclear whether active surveillance is a safe option for African American men. Objective: To compare clinical outcomes of African American and non-Hispanic White men with low-risk prostate cancer managed with active surveillance. Design, Setting, and Participants: Retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The date of final follow-up was March 31, 2020. Exposures: Active surveillance was defined as no definitive treatment within the first year of diagnosis and at least 1 additional surveillance biopsy. Main Outcomes and Measures: Progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality. Results: The cohort included 8726 men, including 2280 African American men (26.1%) (median age, 63.2 years) and 6446 non-Hispanic White men (73.9%) (median age, 65.5 years), and the median follow-up was 7.6 years (interquartile range, 5.7-9.9; range, 0.2-19.2). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence of disease progression was 59.9% vs 48.3% (difference, 11.6% [95% CI, 9.2% to 13.9%); P < .001); of receipt of definitive treatment, 54.8% vs 41.4% (difference, 13.4% [95% CI, 11.0% to 15.7%]; P < .001); of metastasis, 1.5% vs 1.4% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .49); of prostate cancer-specific mortality, 1.1% vs 1.0% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .82); and of all-cause mortality, 22.4% vs 23.5% (difference, 1.1% [95% CI, -0.9% to 3.1%]; P = 0.09). Conclusions and Relevance: In this retrospective cohort study of men with low-risk prostate cancer followed up for a median of 7.6 years, African American men, compared with non-Hispanic White men, had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment, but not metastasis or prostate cancer-specific mortality. Longer-term follow-up is needed to better assess the mortality risk.

African-American men with low-risk prostate cancer treated with radical prostatectomy in an equal-access health care system: implications for active surveillance.

BACKGROUND: There is concern that African-American men (AA) with low-risk prostate cancer may present with more aggressive disease and thus may not be candidates for active surveillance (AS). However, it is uncertain if poorer outcomes are due to disparities in access to medical care rather than true biological differences. METHODS: Observational cohort study of patients diagnosed with low-risk PC-Gleason score ≤6, clinical tumor stage ≤2A, and prostate specific antigen (PSA) level ≤10-at US Department of Veterans Affairs between January 1, 2001 and October 31, 2015 and treated with radical prostatectomy. Outcomes included upgrading to Gleason Grade Group 2 (GG2), GG ≥ 3, PSA recurrence, pathologic tumor stage ≥3, positive surgical margins, and all-cause mortality. RESULTS: A total of 2857 men (AA: 835 White: 2022) with a median follow-up of 7.1 years. Overall, there was no significant difference between AA and White men in upgrading to GG ≥ 3 (RR = 1.18, p = 0.43), tumor stage ≥3 (RR = 0.95, p = 0.74), positive surgical margins (RR = 1.14, p = 0.20), PSA recurrence (SHR = 1.26, p = 0.06), and all-cause mortality (SHR = 1.26, p = 0.16). However, there was a significant increase in upgrading for AA to GG2 (RR = 1.49, p < 0.01). CONCLUSIONS: There was no significant difference in most adverse pathologic outcomes between AA and White patients. However, GG2 upgrading was more common in AA men. The implication is that AA may need to undergo additional evaluation, such as a biopsy MRI, before initiating AS. Whether the increase in GG2 upgrading will lead to poorer long-term clinical outcomes such as metastasis and PCSM also requires further investigation.

A Matched Case-Control Analysis of Clinical Outcomes for Patients With Inflammatory Bowel Disease and Rectal Cancer Treated With Pelvic Radiation Therapy.

PURPOSE: Inflammatory bowel disease (IBD) is a known risk factor for rectal cancer, and RT is often an important part of therapy for these patients. Previously published studies have raised concerns for increased rates of RT toxicity in patients with IBD. We performed a matched case-control analysis to assess RT-related toxicity in a large sample of U.S. veterans afflicted with IBD and rectal cancer. METHODS AND MATERIALS: We identified 186 veterans with rectal cancer (71 Patients with IBD treated with RT, 71 matched controls without IBD treated with RT, and 44 nonmatched controls with IBD treated without RT) diagnosed between 2000 and 2015. We analyzed short- and long-term toxicity and mortality in multivariable logistic regression, Fine-Gray, and frailty models, adjusting for potential confounders. RESULTS: When comparing patients with and without IBD treated with RT there were no differences in RT breaks (adjusted odds ratio [aOR], 1.70; 95% confidence interval [CI], 0.38-4.76; P = .49) or the need for antidiarrheal medication during RT (aOR, 1.53; 95% CI, 0.70-3.35; P = .29). There was a trend toward higher risk of hospital admission during RT for RT + patients with IBD (aOR, 2.69; 95% CI, 0.88-8.22; P = .08). There were higher rates of small bowel obstruction (OR, 15; 95% CI, 1.9-115; P = .009) and a trend toward higher rates of abdominopelvic adhesions (OR, 3.6; 95% CI, 0.98-13; P = .05) in the RT + IBD cohort. However, compared with a nonmatched cohort of patients with IBD treated without RT there were no differences in long-term complications. No differences were found in other acute or long-term toxicities. Rectal cancer-specific mortality appeared similar across all cohorts. CONCLUSIONS: RT does not appear to increase the rates of acute or long-term toxicity in patients with IBD and should be considered a standard part of therapy when otherwise indicated.

Stroke and thromboembolic events in men with prostate cancer treated with definitive radiation therapy with or without androgen deprivation therapy.

BACKGROUND: There is conflicting evidence regarding the association between androgen deprivation therapy (ADT) for prostate cancer (PC) and the risk of developing stroke and thromboembolic events. Our study evaluated the association between ADT use and development of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), and pulmonary embolism (PE) in a homogenous group of men with PC treated with definitive radiation therapy (RT) after controlling for multiple sources of confounding. METHODS: Observational cohort study of patients diagnosed with PC at the US Department of Veterans Affairs between 1 January 2001 and October 31, 2015 and treated with definitive RT. Exposure was initiation of ADT within 1 year of PC diagnosis. Primary outcomes were development of stroke, TIA, DVT, or PE. RESULTS: 44,246 men with median follow-up of 6.8 years. The overall cumulative incidences of stroke, TIA, DVT, and PE at 10 years were 6.0, 3.0, 3.4, and 1.9%, respectively. In the multivariable competing risks model, there was a significant association between ADT and stroke (subdistribution hazard ratio (SHR) = 1.19, 95% CI = 1.09-1.30, p < 0.01), TIA (SHR = 1.24, 95% CI = 1.08-1.41, p < 0.01), and DVT (SHR = 1.18, 95% CI = 1.04-1.34, p < 0.01). ADT was only associated with PE in men receiving ADT for > 1 year (SHR = 1.34, 95% CI = 1.06-1.69, p-value = 0.03). CONCLUSION: We observed an increase in the risk of stroke, TIA, and DVT in men receiving ADT and an increased risk of PE in men receiving long-term ADT. These results highlight concerns regarding long-term risks of ADT on stroke and thromboembolic events in the treatment of PC.

Androgen deprivation therapy and depression in men with prostate cancer treated with definitive radiation therapy.

BACKGROUND: There is no consensus on the association between the use of androgen deprivation therapy (ADT) and the risk of developing depression. This study investigated the association between ADT use and the development of depression, outpatient psychiatric services, inpatient psychiatric services, and suicide in a homogeneous group of men with prostate cancer (PC) treated with definitive radiation therapy (RT) after controlling for multiple sources of selection bias. METHODS: This was a retrospective, observational cohort study of 39,965 veterans with PC who were treated with definitive RT and were diagnosed by the US Department of Veterans Affairs health care system between January 1, 2001, and October 31, 2015. Exposure was ADT initiation within 1 year of the PC diagnosis. The primary outcome was new development of depression. Secondary outcomes were outpatient psychiatric use, inpatient psychiatric use, and suicide. RESULTS: During follow-up, 934 patients were newly diagnosed with depression, 7825 patients used outpatient psychiatric services, 358 patients used inpatient psychiatric services, and 54 patients committed suicide. In the multivariable competing risks regression model, ADT was associated with the development of depression (subdistribution hazard ratio [SHR], 1.50; 95% confidence interval [CI], 1.32-1.71; P < .001). ADT was also associated with outpatient psychiatric utilization (SHR, 1.21; 95% CI, 1.16-1.27; P < .001). Finally, ADT was not associated with inpatient psychiatric utilization or suicide. CONCLUSIONS: An increase in the risk of depression and the use of outpatient psychiatric services was observed in a large cohort of men with PC who received ADT with definitive RT. These results may provide further evidence for the long-term risks of ADT for psychiatric health in the treatment of PC.

Infliximab for treatment-refractory transverse myelitis following immune therapy and radiation.

BACKGROUND: Neurologic toxicities with immune therapy are rare, but can cause devastating and often permanent injury when they occur. Although there is increasing interest in the potential synergism between immune therapy and radiation, it is possible that such combinations may lead to a greater number or increased severity of immune-related adverse events. We present here a case of extensive and progressive transverse myelitis following combined therapy, which did not improve until treatment with infliximab. This case highlights the unmet need for treatment of adverse events that are refractory to consensus recommendations, and may ultimately require further study and incorporation into future published guidelines. CASE PRESENTATION: We report a case of a 68-year-old with metastatic melanoma, who developed transverse myelitis in the setting of immune checkpoint blockade and spinal irradiation for vertebral metastases. Despite management according to published consensus guidelines: cessation of immune therapy, high-dose steroids, and plasmapheresis, he continued to deteriorate neurologically, and imaging revealed a progressive and ascending transverse myelitis. The patient was then treated with infliximab, and demonstrated dramatic imaging and modest clinical improvement following the first treatment cycle. CONCLUSIONS: This is the first report describing the successful use of infliximab in immune therapy and radiation-related transverse myelitis that was not responding to recommended therapy. Evaluation of additional treatment options such as infliximab for high-grade immune-related neurologic toxicities is warranted, and may be needed earlier in the disease process to prevent significant morbidity. The adverse effects of immune therapy when used in combination with radiation also require further investigation.

Intensity Modulated Radiation Therapy Versus Conventional Radiation for Anal Cancer in the Veterans Affairs System.

PURPOSE: Compared with conventional radiation therapy, intensity modulated radiation therapy (IMRT) may reduce acute toxicity from anal cancer treatment, potentially leading to improved long-term outcomes. We analyze the effect of IMRT on short- and long-term outcomes among a large sample of US veterans. METHODS AND MATERIALS: From a national Veterans Affairs database, we identified 779 patients (n = 403 conventional radiation therapy, n = 376 IMRT) with locally advanced anal squamous cell carcinoma diagnosed between 2000 and 2015 and treated with concurrent chemoradiation therapy. Radiation treatment planning and dosimetric constraints were not standardized across patients. We analyzed the effect of IMRT on short-term outcomes (acute toxicity, treatment breaks, and incomplete chemotherapy) and long-term outcomes (survival and ostomy placement) in multivariable logistic regression, Fine-Gray, and frailty models, adjusting for potential confounders. RESULTS: IMRT was associated with decreased radiation treatment breaks ≥5 days (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.37-0.91; P = .02), increased rates of receiving 2 cycles of mitomycin C chemotherapy (OR 2.04; 95% CI 1.22-3.45; P = .007), increased rates of receiving 2 cycles of any chemotherapy (OR 3.45; 95% CI 1.82-6.25; P < .001), and decreased risk of ostomy related to tumor recurrence or progression (subdistribution hazard ratio 0.60; 95% CI 0.37-0.99; P = .045). IMRT was not associated with a decrease in grade 3 to 4 hematologic toxicity (P = .79), hospitalization for gastrointestinal toxicity (P = .59), or cancer-specific survival (P = 0.18). CONCLUSIONS: Among a large sample of US veterans with anal cancer, IMRT was associated with higher rates of receiving 2 chemotherapy cycles, decreased radiation treatment breaks, and decreased rates of ostomy placement. IMRT appears to offer substantial benefits over conventional radiation therapy for patients undergoing concurrent chemoradiation therapy for anal cancer.

Clinical Impact of Local Progression in Pancreatic Cancer.

Background: The high prevalence of distant metastatic disease among patients with pancreatic cancer often draws attention away from the local pancreatic tumor. This study aimed to define the complications and hospitalizations from local versus distant disease progression among a retrospective cohort of patients with pancreatic cancer. Methods: Records of 298 cases of pancreatic cancer treated at a single institution from 2004 through 2015 were retrospectively reviewed, and cancer-related symptoms and complications requiring hospitalization were recorded. Hospitalizations related to pancreatic cancer were attributed to either local or distant progression. Cumulative incidence analyses were used to estimate the incidence of hospitalization, and multivariable Fine-Gray regression models were used to identify factors predictive of hospitalizations. Results: The 1-year cumulative incidences of hospitalization due to local versus distant disease progression were 31% and 24%, respectively. Among 509 recorded hospitalizations, leading local etiologies included cholangitis (10%), biliary obstruction (7%), local procedure complication (7%), and gastrointestinal bleeding (7%). On multivariable analysis, significant predictors of hospitalization from local progression included unresectable disease (subdistribution hazard ratio [SDHR], 2.42; P<.01), black race (SDHR, 3.34; P<.01), younger age (SDHR, 1.02 per year; P=.01), tumor in the pancreatic head (SDHR, 2.19; P<.01), and larger tumor size (SDHR, 1.13 per centimeter; P=.02). Most patients who died in the hospital from pancreatic cancer (56%) were admitted for complications of local disease progression. Conclusions: Patients with pancreatic cancer experience significant complications of local tumor progression. Although distant metastatic progression represents a hallmark of pancreatic cancer, future research should also focus on improving local therapies.

Three-month posttreatment prostate-specific antigen level as a biomarker of treatment response in patients with intermediate-risk or high-risk prostate cancer treated with androgen deprivation therapy and radiotherapy.

BACKGROUND: Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS). METHODS: A total of 5783 patients with intermediate-risk or high-risk localized prostate cancer who were diagnosed between 2000 and 2015 and treated with RT and androgen deprivation therapy were identified from Veterans Affairs data. Patients were divided into groups based on 3-month post-RT PSA values: <0.10 ng/mL, 0.10 to 0.49 ng/mL, and ≥0.50 ng/mL. The effect of the 3-month PSA group on bPFS, PCSS, and OS was evaluated in multivariable Cox models adjusting for potential confounders. RESULTS: There were 2651 patients with intermediate-risk and 3132 with high-risk disease; approximately 11% had a 3-month PSA level of ≥0.50 ng/mL. A higher 3-month PSA level was found to be strongly associated with each outcome; compared with patients in the group with a 3-month PSA value <0.10 ng/mL, the authors noted greater hazards for the patients with a 3-month PSA value ≥0.50 ng/mL (hazard ratio for bPFS: 5.23; PCSS: 3.97; and OS: 1.50 [P<.001 for all]) and the patients with a 3-month PSA value of 0.10 to 0.49 ng/mL (hazard ratio for bPFS: 2.41 [P<.001]; PCSS: 2.29 [P<.001]; and OS: 1.21 [P = .003]). When analyzed separately, the 3-month PSA level was found to be predictive of OS in the high-risk group (P<.001) but not the intermediate-risk group (P = .21). CONCLUSIONS: The 3-month post-RT PSA level appears to be a strong prognostic biomarker for bPFS, PCSS, and OS in patients with intermediate-risk and high-risk prostate cancer, particularly those with high-risk disease. The 3-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate endpoint in clinical trials. Cancer 2018;124:2939-47. © 2018 American Cancer Society.

4π plan optimization for cortical-sparing brain radiotherapy.

BACKGROUND AND PURPOSE: Incidental irradiation of normal brain tissue during radiotherapy is linked to cognitive decline, and may be mediated by damage to healthy cortex. Non-coplanar techniques may be used for cortical sparing. We compared normal brain sparing and probability of cortical atrophy using 4π radiation therapy planning vs. standard fixed gantry intensity-modulated radiotherapy (IMRT). MATERIAL AND METHODS: Plans from previously irradiated brain tumor patients ("original IMRT", n = 13) were re-planned to spare cortex using both 4π optimization ("4π") and IMRT optimization ("optimized IMRT"). Homogeneity index (HI), gradient measure, doses to cortex and white matter (excluding tumor), brainstem, optics, and hippocampus were compared with matching PTV coverage. Probability of three grades of post-treatment cortical atrophy was modeled based on previously established dose response curves. RESULTS: With matching PTV coverage, 4π significantly improved HI by 27% (p = 0.005) and gradient measure by 8% (p = 0.001) compared with optimized IMRT. 4π optimization reduced mean and equivalent uniform doses (EUD) to all standard OARs, with 14-15% reduction in hippocampal EUD (p ≤ 0.003) compared with the other two plans. 4π significantly reduced dose to fractional cortical volumes (V50, V40 and V30) compared with the original IMRT plans, and reduced cortical V30 by 7% (p = 0.008) compared with optimized IMRT. White matter EUD, mean dose, and fractional volumes V50, V40 and V30 were also significantly lower with 4π (p ≤ 0.001). With 4π, probability of grade 1, 2 and 3 cortical atrophy decreased by 12%, 21% and 26% compared with original IMRT and by 8%, 14% and 3% compared with optimized IMRT, respectively (p ≤ 0.001). CONCLUSIONS: 4π radiotherapy significantly improved cortical sparing and reduced doses to standard brain OARs, white matter, and the hippocampus. This was achieved with superior PTV dose homogeneity. Such sparing could reduce the probability of cortical atrophy that may lead to cognitive decline.

Effect of CD4 Count on Treatment Toxicity and Tumor Recurrence in Human Immunodeficiency Virus-Positive Patients With Anal Cancer.

PURPOSE: To study the effects of immunosuppression on treatment toxicity, long-term cancer recurrence risk, and survival among human immunodeficiency virus (HIV)-positive anal cancer patients. METHODS AND MATERIALS: From a nationwide retrospective cohort of veterans with anal cancer we identified 142 HIV-positive patients with stage I-III disease, diagnosed between 2000 and 2015 and treated with definitive-intent chemotherapy and radiation. We used regression models to study the impact of pretreatment CD4 counts and longitudinal posttreatment CD4 counts on outcomes including acute toxicity, long-term ostomy rates, cancer recurrence, cancer-specific survival, and overall survival. All models were adjusted for potential confounders. RESULTS: The median pretreatment CD4 count was 375 cells/mm3, which dropped to 157 cells/mm3 after treatment. Each 100-cell/mm3 decrease in pretreatment CD4 count was associated with an increased risk of acute hematologic toxicity (odds ratio 1.19, 95% confidence interval [CI] 1.01-1.42, P=.04) and hospitalization for hematologic toxicity (odds ratio 1.24, 95% CI 1.00-1.54, P=.049) but not gastrointestinal toxicity, tumor recurrence, or cancer-specific mortality (P>.05). Each 100-cells/mm3 decrease in posttreatment CD4 count increased the risk of recurrence by 54% (hazard ratio 1.54, 95% CI 1.09-2.17, P=.01) and cancer mortality by 46% at a trend level (hazard ratio 1.46, 95% CI 0.99-2.14, P=.06). Neither pre- nor posttreatment CD4 count influenced long-term ostomy rates or overall survival (all P>.05). CONCLUSIONS: Lower pretreatment CD4 counts were associated with acute hematologic toxicity, and lower posttreatment CD4 count levels were associated with an increased risk of tumor recurrence. These results suggest that immune surveillance may play an important role in long-term disease control in anal cancer.

Distortion inherent to magnetic resonance imaging can lead to geometric miss in radiosurgery planning.

PURPOSE: Anatomic distortion is present in all magnetic resonance imaging (MRI) data because of nonlinearity of gradient fields; it measures up to several millimeters. We evaluated the potential for uncorrected MRI to lead to geometric miss of the target volume in stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Twenty-eight SRS cases were studied retrospectively. MRI scans were corrected for gradient nonlinearity distortion in 3 dimensions, and gross tumor volumes (GTVs) were contoured. The manufacturer-specified distortion field was then reapplied to GTV masks to allow measurement of GTV displacement in uncorrected images. The uncorrected GTV was used for SRS planning, and the dose received by the true (corrected) GTV was measured. RESULTS: Median displacement of the GTV resulting from gradient distortion was 1.2 mm (interquartile range, 0.1-2.3 mm), with a minimum of 0 mm and a maximum of 3.9 mm. Eight of the 28 cases met a priori criteria for "geometric miss." CONCLUSIONS: Although MRI distortion is often subtle on visual inspection, there is a significant clinical impact of this distortion on SRS planning. Distortion-corrected MRI should uniformly be used for intracranial radiosurgery planning because uncorrected MRI can lead to potential geometric miss.

Clinical Outcomes of Computed Tomography-Based Volumetric Brachytherapy Planning for Cervical Cancer.

PURPOSE/OBJECTIVES: A report of clinical outcomes of a computed tomography (CT)-based image guided brachytherapy (IGBT) technique for treatment of cervical cancer. METHODS AND MATERIALS: Seventy-six women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma diagnosed between 2007 and 2014 were treated with definitive external beam radiation therapy (EBRT) with or without concurrent chemotherapy followed by high-dose-rate (HDR) IGBT. All patients underwent planning CT simulation at each implantation. A high-risk clinical target volume (HRCTV) encompassing any visible tumor and the entire cervix was contoured on the simulation CT. When available, magnetic resonance imaging (MRI) was performed at implantation to assist with tumor delineation. The prescription dose was prescribed to the HRCTV. RESULTS: The median follow-up time was 17 months. Thirteen patients (17%) had an MRI done before brachytherapy, and 16 patients (21%) were treated without MRI guidance. The mean EBRT/IGBT sum 2-Gy equivalent dose (EQD2) delivered to the 90% volume of the HRCTV was 86.3 Gy. The mean maximum EQD2s delivered to 2 cm(3) of the rectum, sigmoid, and bladder were 67.5 Gy, 66.2 Gy, and 75.3 Gy, respectively. The 2-year cumulative incidences of local, locoregional, and distant failure were 5.8% (95% confidence interval [CI]: 1.4%-14.8%), 15.1% (95% CI: 5.4%-29.4%), and 24.3% (95% CI: 12.1%-38.9%), respectively. The 2-year overall and disease-free survival rates were 75% (95% CI, 61%-91%) and 73% (95% CI, 60%-90%), respectively. Twenty-nine patients (38%) experienced grade ≥ 2 acute toxicity, with 5 cases of acute grade 3 toxicity and no grade ≥ 4 toxicities. One patient experienced grade 3 gastrointestinal toxicity. No other late grade ≥ 3 events were observed. CONCLUSIONS: This is the largest report to date of CT/MRI-based IGBT for the treatment of cervical cancer. The results are promising, with excellent local control and acceptable toxicity. Further investigation is needed to assess the long-term safety and efficacy of this treatment.

Single-Isocenter Frameless Volumetric Modulated Arc Radiosurgery for Multiple Intracranial Metastases.

BACKGROUND: Stereotactic radiosurgery (SRS) is a well-accepted treatment for patients with intracranial metastases, but outcomes with volumetric modulated arc radiosurgery (VMAR) are poorly described. OBJECTIVE: To report our initial clinical experience applying a novel single-isocenter technique to frameless VMAR for simultaneous treatment of multiple intracranial metastases. METHODS: We performed a retrospective analysis of 15 patients undergoing frameless VMAR for multiple intracranial metastases using a single, centrally located isocenter in the period 2009 and 2011. Of these, 3 patients were treated for progressive or recurrent intracranial disease. A total of 62 metastases (median, 3 per patient; range, 2-13) were treated to a median dose of 20 Gy (range, 15-30 Gy). Three patients were treated with fractionated SRS. Follow-up including clinical examination and magnetic resonance imaging (MRI) occurred every 3 months. RESULTS: The median follow-up for all patients was 7.1 months (range, 1.1-24.3), with 11 patients (73.3%) followed until death. For the remaining 4 patients alive at the time of analysis, the median follow-up was 19.6 months (range, 9.2-24.3). Local control at 6 and 12 months was 91.7% (95% confidence interval [CI], 84.6%-100.0%) and 81.5% (95% CI, 67.9%-100.0%), respectively. Regional failure was observed in 9 patients (60.0%), and 7 patients (46.7%) received salvage therapy. Overall survival at 6 months was 60.0% (95% CI, 40.3%-88.2%). Grade 3 or higher treatment-related toxicity was not observed. The median total treatment time was 7.2 minutes (range, 2.8-13.2 minutes). CONCLUSION: Single-isocenter, frameless VMAR for multiple intracranial metastases is a promising technique that may provide similar clinical outcomes compared with conventional radiosurgery.