Patterns of Recurrence After Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation.

BACKGROUND: Improved treatment strategies are needed for patients with locally advanced gastric cancer with poor response to neoadjuvant chemotherapy. We aimed to describe patterns of failure for patients with no or partial response (NR, PR) to preoperative chemotherapy. PATIENTS AND METHODS: We analyzed patients with locally advanced gastric cancer treated from 2008 to 2022 with preoperative chemotherapy followed by surgery with D2 resection. We excluded patients who received radiation. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated. For patients with recurrent abdominal disease, hypothetical radiation clinical treatment volumes (CTV) were contoured on postoperative scans and compared with patterns of recurrence. RESULTS: A total of 60 patients were identified. The most used preoperative chemotherapy was FLOT (38.6%), followed by FOLFOX (30%) and ECF/ECX/EOX (23.3%). Four (6.7%), 40 (66.7%), and 9 patients (15%) had a complete pathologic response (CR), PR, and NR to neoadjuvant therapy, respectively. Among patients without a CR, 3-year overall and progression-free survival rates were 62.3% (95% CI 48-76.6%) and 51.3% (95% CI 36.9-65.7%), respectively. Three-year cumulative incidence of LRF and DM were 8.4% (95% CI 0.4-16.4%) and 41.0% (95% CI 26.3-55.4%), respectively. Absolute rates of patients having the first site of recurrence encompassed by a postoperative radiation CTV was 2.0% for patients without a CR and 0% for patients with NR. CONCLUSIONS: Patients with locally advanced gastric cancer with less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival.

Validation of a Resectability Scoring System for Prediction of Pancreatic Adenocarcinoma Surgical Outcomes.

BACKGROUND: The most used pancreatic cancer (PC) resectability criteria are descriptive in nature or based solely on dichotomous degree of involvement (< 180° or > 180°) of vessels, which allows for a high degree of subjectivity and inconsistency. METHODS: Radiographic measurements of the circumferential degree and length of tumor contact with major peripancreatic vessels were retrospectively obtained from pre-treatment multi-detector computed tomography (MDCT) images from PC patients treated between 2001 and 2015 at two large academic institutions. Arterial and venous scores were calculated for each patient, then tested for a correlation with tumor resection and R0 resection. RESULTS: The analysis included 466 patients. Arterial and venous scores were highly predictive of resection and R0 resection in both the training (n = 294) and validation (n = 172) cohorts. A recursive partitioning tree based on arterial and venous score cutoffs developed with the training cohort was able to stratify patients of the validation cohort into discrete groups with distinct resectability probabilities. A refined recursive partitioning tree composed of three resectability groups was generated, with probabilities of resection and R0 resection of respectively 94 and 73% for group A, 61 and 35% for group B, and 4 and 2% for group C. This resectability scoring system (RSS) was highly prognostic, predicting median overall survival times of 27, 18.9, and 13.5 months respectively for patients in RSS groups A, B, and C (p < 0.001). CONCLUSIONS: The proposed RSS was highly predictive of resection, R0 resection, and prognosis for patients with PC when tested against an external dataset.

Practical Guideline for Prevention of Patchy Hair Loss following CyberKnife Stereotactic Radiosurgery for Calvarial or Scalp Tumors: Retrospective Analysis of a Single Institution Experience.

INTRODUCTION: Patchy alopecia is a common adverse effect of stereotactic radiosurgery (SRS) on the calvarium and/or scalp, yet no guidelines exist for its prevention. This study aims to investigate the incidence and outcomes of patchy alopecia following SRS for patients with calvarial or scalp lesions and establish preventive guidelines. METHODS: The study included 20 patients who underwent CyberKnife SRS for calvarial or scalp lesions, resulting in a total of 30 treated lesions. SRS was administered as a single fraction for 8 lesions and hypofractionated for 22 lesions. The median SRS target volume was 9.85 cc (range: 0.81-110.7 cc), and the median prescription dose was 27 Gy (range: 16-40 Gy), delivered in 1-5 fractions (median: 3). The median follow-up was 15 months. RESULTS: Among the 30 treated lesions, 11 led to patchy alopecia, while 19 did not. All cases of alopecia resolved within 12 months, and no patients experienced other adverse radiation effects. Lesions resulting in alopecia exhibited significantly higher biologically effective dose (BED) and single-fraction equivalent dose (SFED) on the overlying scalp compared to those without alopecia. Patients with BED and SFED exceeding 60 Gy and 20 Gy, respectively, were 9.3 times more likely to experience patchy alopecia than those with lower doses. The 1-year local tumor control rate for the treated lesions was 93.3%. Chemotherapy was administered for 26 lesions, with 11 lesions receiving radiosensitizing agents. However, no statistically significant difference was found. CONCLUSION: In summary, SRS is a safe and effective treatment for patients with calvarial/scalp masses regarding patchy alopecia near the treated area. Limiting the BED under 60 Gy and SFED under 20 Gy for the overlying scalp can help prevent patchy alopecia during SRS treatment of the calvarial/scalp mass. Clinicians can use this information to inform patients about the risk of alopecia and the contributing factors.

Stereotactic radiosurgery for sarcoma metastases to the brain: a single-institution experience.

OBJECTIVE: Brain metastases (BMs) secondary to sarcoma are rare, and their incidence ranges from 1% to 8% of all bone and soft tissue sarcomas. Although stereotactic radiosurgery (SRS) is widely used for BMs, only a few papers have reported on SRS for sarcoma metastasizing to the brain. The purpose of this study was to evaluate the safety and effectiveness of SRS for sarcoma BM. METHODS: The authors retrospectively reviewed the clinical and radiological outcomes of patients with BM secondary to histopathologically confirmed sarcoma treated with SRS, either as primary treatment or as adjuvant therapy after surgery, at their institution between January 2005 and September 2022. They also compared the outcomes of patients with hemorrhagic lesions and of those without. RESULTS: Twenty-three patients (9 females) with 150 BMs secondary to sarcoma were treated with CyberKnife SRS. Median age at the time of treatment was 48.22 years (range 4-76 years). The most common primary tumor sites were the heart, lungs, uterus, upper extremities, chest wall, and head and neck. The median Karnofsky Performance Status on presentation was 73.28 (range 40-100). Eight patients underwent SRS as a primary treatment and 15 as adjuvant therapy to the resection cavity. The median tumor volume was 24.1 cm3 (range 0.1-150.3 cm3), the median marginal dose was 24 Gy (range 18-30 Gy) delivered in a median of 1 fraction (range 1-5) to a median isodose line of 76%. The median follow-up was 8 months (range 2-40 months). Median progression-free survival and overall survival were 5.3 months (range 0.4-32 months) and 8.2 months (range 0.1-40), respectively. The 3-, 6-, and 12-month local tumor control (LTC) rates for all lesions were respectively 78%, 52%, and 30%. There were no radiation-induced adverse effects. LTC at the 3-, 6-, and 12-month follow-ups was better in patients without hemorrhagic lesions (100%, 70%, and 40%, respectively) than in those with hemorrhagic lesions (68%, 38%, and 23%, respectively). CONCLUSIONS: SRS, both as a primary treatment and as adjuvant therapy to the resection cavity after surgery, is a safe and relatively effective treatment modality for sarcoma BMs. Nonhemorrhagic lesions show better LTC than hemorrhagic lesions. Larger studies aiming to validate these results are encouraged.

Stereotactic radiosurgery for distant brain metastases secondary to esthesioneuroblastoma: a single-institution series.

OBJECTIVE: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication. METHODS: A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported. RESULTS: Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects. CONCLUSIONS: In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.

Socio-economic disparities influence likelihood of post-operative radiation to resection cavities of metastatic brain tumors.

PURPOSE: Irradiating the surgical bed of resected brain metastases improves local and distant disease control. Over time, stereotactic radiosurgery (SRS) has replaced whole brain radiotherapy (WBRT) as the treatment standard of care because it minimizes long-term damage to neuro-cognition. Despite this data and growing adoption, socio-economic disparities in clinical access can result in sub-standard care for some patient populations. We aimed to analyze the clinical and socio-economic characteristics of patients who did not receive radiation after surgical resection of brain metastasis. METHODS: Our sample was obtained from Clinformatics® Data Mart Database and included all patients from 2004 to 2021 who did or did not receive radiation treatment within sixty days after resection of tumors metastatic to the brain. Regression analysis was done to identify factors responsible for loss to adjuvant radiation treatment. RESULTS: Of 8362 patients identified who had undergone craniotomy for resection of metastatic brain tumors, 3430 (41%) patients did not receive any radiation treatment. Compared to patients who did receive some form of radiation treatment (SRS or WBRT), patients who did not get any form of radiation were more likely to be older (p = 0.0189) and non-white (p = 0.008). Patients with Elixhauser Comorbidity Index ≥3 were less likely to receive radiation treatment (p < 0.01). Fewer patients with household income ≥ $75,000 did not receive radiation treatment (p < 0.01). CONCLUSION: Age, race, household income, and comorbidity status were associated with differential likelihood to receive post-operative radiation treatment.

Radiation Oncology Virtual Education Rotation (ROVER) 2.0 for Residents: Implementation and Outcomes.

The COVID-19 pandemic catalyzed the integration of a virtual education curriculum to support radiation oncologists in training. We report outcomes from Radiation Oncology Virtual Education Rotation (ROVER) 2.0, a supplementary virtual educational curriculum created for radiation oncology residents globally. A prospective cohort of residents completed surveys before and after the live virtual webinar sessions (pre- and post-surveys, respectively). Live sessions were structured as complex gray-zone cases across various core disease sites. Resident demographics and responses were summarized using means, standard deviations, and proportions. Nine ROVER sessions were held from October 2020 to June 2021. A total of 1487 registered residents completed the pre-survey, of which 786 attended the live case discussion and 223 completed post-surveys. A total of 479 unique radiation oncology residents (of which 95, n = 19.8%, were international attendees) from 147 institutions (national, n = 81, 55.1%; international, n = 66, 44.9%) participated in the sessions. There was similar participation across post-graduate year (PGY) 2 through 5 (range n = 86 to n = 105). Of the 122 unique resident post-surveys, nearly all reported learning through the virtual structure as "very easy" or "easy" (97.5%, n = 119). A majority rated the ROVER 2.0 educational sessions to be "valuable or "very valuable" (99.2%, n = 121), and the panelists-attendee interaction as "appropriate" (97.5%, n = 119). Virtual live didactics aimed at radiation oncology residents are feasible. These results suggest that the adoption of the ROVER 2.0 curricula may help improve radiation oncology resident education.

Impact of socio-economic factors on radiation treatment after resection of metastatic brain tumors: trends from a private insurance database.

BACKGROUND: Stereotactic radiosurgery (SRS) to the surgical bed of resected brain metastases is now considered the standard of care due to its advantages over whole brain radiation therapy (WBRT). Despite the upward trend in SRS adoption since the 2000s, disparities have been reported suggesting that socio-economic factors can influence SRS utilization. OBJECTIVE: To analyze recent trends in SRS use and identify factors that influence treatment. METHODS: We conducted a retrospective cohort study with the Optum Commercial Claims and Encounters Database and included all patients from 2004 to 2021 who received SRS or WBRT within 60 days after resection of tumors metastatic to the brain. RESULTS: A total of 3495 patients met the inclusion and exclusion criteria. There were 1998 patients in the SRS group and 1497 patients in the WBRT group. SRS use now supersedes WBRT by a wide margin. Lung, breast and colon were the most common sites of primary tumor. Although we found no significant differences based on race among the treatment groups, patients with annual household income greater than $75,000 and those with some college or higher education are significantly more likely to receive SRS (OR 1.44 and 1.30; 95% CI 1.18-1.76 and 1.08-1.56; P = 0.001 and 0.005, respective). Patients with Elixhauser Comorbidity Index of three or more were significantly more likely to receive SRS treatment. CONCLUSION: The use of post-surgical SRS for brain metastasis has increased significantly over time, however education and income were associated with differential SRS utilization.

Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer.

PURPOSE: Although osimertinib has excellent intracranial activity in metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or L858R EGFR alterations, measures of local control of brain metastases are less well-reported. We describe lesion-level outcomes of brain metastases treated with osimertinib alone. METHODS: We retrospectively reviewed patients with EGFR-mutant NSCLC with untreated brain metastasis measuring ≥ 5 mm at the time of initiating osimertinib. Cumulative incidence of local recurrence in brain (LRiB) was calculated with death as a competing risk, and univariable and multivariable analyses were conducted to identify factors associated with LRiB. RESULTS: We included 284 brain metastases from 37 patients. Median follow-up was 20.1 months. On initial MRI after starting osimertinib, patient-level response was complete response (CR) in 11 (15%), partial response (PR) in 33 (45%), stable disease (SD) in 18 (25%) and progressive disease (PD) in 11 (15%). The 1-year cumulative incidence of LRiB was 14% (95% CI 9.9-17.9) and was significantly different in patients with a CR (0%), PR (4%), and SD (11%; p = 0.02). Uncontrolled primary tumor (adjusted hazard ratio [aHR] 3.78, 95% CI 1.87-7.66; p < 0.001), increasing number of prior systemic therapies (aHR 2.12, 95% CI 1.49-3.04; p < 0.001), and higher ECOG score (aHR 7.8, 95% CI 1.99-31.81; p = 0.003) were associated with LRiB. CONCLUSIONS: Although 1-year cumulative incidence of LRiB is < 4% with a CR or PR, 1-year cumulative incidence of LRiB is over 10% for patients with less than a PR to osimertinib on initial MRI. These patients should be followed closely for need for additional treatment such as stereotactic radiosurgery.

Greater financial toxicity relates to greater distress and worse quality of life among breast and gynecologic cancer survivors.

BACKGROUND: Financial toxicity includes distress and burden from cancer-related costs. Women are more likely to experience worse cancer-related financial outcomes than men. This study evaluated breast and gynecologic cancer patients' subjective experiences of financial toxicity and associations with distress and quality of life (QOL). METHODS: A cross-sectional survey study included measures of financial toxicity (Comprehensive Score for Financial Toxicity [COST] Version 2), distress (Patient Health Questionnaire), and QOL (Functional Assessment of Cancer Therapy). Chi-square, t-tests, and ANOVAs examined bivariate relationships. Two regression models tested associations between financial toxicity and distress and QOL, controlling for covariates. Financial toxicity subgroups were compared based on a validated grading system. RESULTS: Participants (N = 273; 74% breast cancer) averaged 54.65 years (SD = 12.08), were 3.42 years (SD = 4.20) post-diagnosis, and 33% reported cancer-related change in employment status. Financial toxicity was "mild" overall (COST M = 26.11, SD = 11.14); 32% worried about cancer-related financial problems (quite a bit/very much; item-level analysis). Worse financial toxicity related to younger age (p < 0.001), identifying as a non-Asian minority (p = 0.03) or Hispanic (p = 0.01), being single (p < 0.001), lower education (p = 0.004), lower income (p < 0.001), late-stage disease (p = 0.001), recurrent disease (p = 0.004), and active treatment (p < 0.001). In separate multivariable models, greater financial toxicity related to greater distress (ß = -0.45 p < 0.001) and worse QOL (ß = 0.58, p < 0.001). Financial toxicity subgroups reported clinically significant differences in distress and QOL (p's < 0.05). CONCLUSIONS: Cancer-related financial burden is associated with pervasive negative effects and may impact subgroups differently. Future research should explore financial experiences across subgroups, aiming to better identify those at risk and build targeted interventions.

Stereotactic radiosurgery for trigeminal neuralgia secondary to tumor: a single-institution retrospective series.

OBJECTIVE: Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution's experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e., the trigeminal nerve, offending tumor, or both. METHODS: Between the years 2009 and 2021, 21 patients with TN secondary to benign (n = 13) or malignant (n = 8) tumors underwent SRS. Barrow Neurological Institute (BNI) pain intensity scale scores were collected from patient electronic medical records at baseline, initial follow-up, and 1 and 3 years post-SRS. The interval change in BNI scale score (ΔBNI) at the various follow-up time points was also calculated to assess the durability of pain relief following SRS. RESULTS: The median follow-up period was 24 (range 0.5-155) months. Five patients (24%) received treatment to the trigeminal nerve only, 10 (48%) received treatment to the tumor only, and 6 (29%) had treatment to both the nerve and tumor. The overall radiation dosage ranged from 14 to 60 Gy delivered in 1-5 fractions, with a median overall dose of 26 Gy. The median dose to the tumor was 22.5 (range 14-35) Gy, delivered in 1-5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 5 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for tumor treatment was 24 Gy in 3 fractions. The median biologically effective dose (with an assumed alpha/beta ratio of 10 [BED10]) for tumor treatments was 43.1 (range 13.3-60.0) Gy. There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets: trigeminal nerve only, tumor only, or both (p = 0.04). At the time of last follow-up, the median ΔBNI score after SRS to the nerve only was -1, 0 after SRS to tumor only, and -2 after SRS to both targets. CONCLUSIONS: SRS offers clinical symptomatic benefit to patients with TN secondary to tumor. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

Stereotactic radiosurgery for recurrent pediatric brain tumors: clinical outcomes and toxicity.

OBJECTIVE: Recurrence of brain tumors in children after the initial course of treatment remains a problem. This study evaluated the efficacy and safety of reirradiation using stereotactic radiosurgery (SRS) in patients with recurrent pediatric primary brain tumors. METHODS: This IRB-approved retrospective review included pediatric patients with recurrent primary brain tumors treated at Stanford University from 2000 to 2019 using frameless SRS. Time to local failure (LF) and distant intracranial failure (DIF) were measured from the date of SRS and analyzed using competing risk analysis. Overall survival (OS) and progression-free survival (PFS) were analyzed with the Kaplan-Meier method. RESULTS: In total, 37 patients aged 2-24 years (median age 11 years at recurrence) were treated for 48 intracranial tumors. Ependymoma (38%) and medulloblastoma (22%) were the most common tumor types. The median (range) single fraction equivalent dose of SRS was 16.4 (12-24) Gy. The median (range) follow-up time was 22.9 (1.5-190) months. The median OS of all patients was 36.8 months. Eight of 40 (20%) lesions with follow-up imaging locally recurred. The 2-year cumulative incidence of LF after reirradiation with SRS was 12.8% (95% CI 4.6%-25.4%). The 2-year cumulative incidence of DIF was 25.3% (95% CI 12.9%-39.8%). The median PFS was 18 months (95% CI 8.9-44). Five (10.4%) patients developed toxicities potentially attributed to SRS, including cognitive effects and necrosis. CONCLUSIONS: Reirradiation using SRS for recurrent pediatric brain tumors appears safe with good local control. Innovations that improve overall disease control should continue because survival outcomes after relapse remain poor.

Longitudinal Analysis of Mental Disorder Burden Among Elderly Patients With Gastrointestinal Malignancies.

BACKGROUND: Patients with cancer are at high risk for having mental disorders, resulting in widespread psychosocial screening efforts. However, there is a need for population-based and longitudinal studies of mental disorders among patients who have gastrointestinal cancer and particular among elderly patients. PATIENTS AND METHODS: We used the SEER-Medicare database to identify patients aged ≥65 years with colorectal, pancreatic, gastric, hepatic/biliary, esophageal, or anal cancer. Earlier (12 months before or up to 6 months after cancer diagnosis) and subsequent mental disorder diagnoses were identified. RESULTS: Of 112,283 patients, prevalence of an earlier mental disorder was 21%, 23%, 20%, 20%, 19%, and 26% for colorectal, pancreatic, gastric, hepatic/biliary, esophageal, and anal cancer, respectively. An increased odds of an earlier mental disorder was associated with pancreatic cancer (odds ratio [OR], 1.17; 95% CI, 1.11-1.23), esophageal cancer (OR, 1.10; 95% CI, 1.02-1.18), and anal cancer (OR, 1.17; 95% CI, 1.05-1.30) compared with colorectal cancer and with having regional versus local disease (OR, 1.09; 95% CI, 1.06-1.13). The cumulative incidence of a subsequent mental disorder at 5 years was 19%, 16%, 14%, 13%, 12%, and 10% for patients with anal, colorectal, esophageal, gastric, hepatic/biliary, and pancreatic cancer, respectively. There was an association with having regional disease (hazard ratio [HR], 1.08; 95% CI, 1.04-1.12) or distant disease (HR, 1.36; 95% CI, 1.28-1.45) compared with local disease and the development of a mental disorder. Although the development of a subsequent mental disorder was more common among patients with advanced cancers, there continued to be a significant number of patients with earlier-stage disease at risk. CONCLUSIONS: This study suggests a larger role for incorporating psychiatric symptom screening and management throughout oncologic care.

Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases.

INTRODUCTION: Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described. METHODS: We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed. RESULTS: A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF. CONCLUSIONS: In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.

Stereotactic radiosurgery for head and neck paragangliomas: a systematic review and meta-analysis.

Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56 years (44-69 years). With a median clinical and radiological follow-up of 44 months (9-161 months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p = 0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r = - 0.4, p = 0.001), right-sided tumor (r = - 0.3, p = 0.03), primary SRS (r = - 0.5, p ≤ 0.001), and initial clinical presentation of hearing loss (r = - 0.4, p = 0.001). To achieve a LC ≥ 90%, a median marginal dose (Gy) of 15 (range, 12-30 Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.

Second cancer risk after primary cancer treatment with three-dimensional conformal, intensity-modulated, or proton beam radiation therapy.

BACKGROUND: The comparative risks of a second cancer diagnosis are uncertain after primary cancer treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam radiotherapy (PBRT). METHODS: Pediatric and adult patients with a first cancer diagnosis between 2004 and 2015 who received 3DCRT, IMRT, or PBRT were identified in the National Cancer Database from 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system. The diagnosis of second cancer was modeled using multivariable logistic regression adjusting for age, follow-up duration, radiotherapy (RT) dose, chemotherapy, sociodemographic variables, and other factors. Propensity score matching also was used to balance baseline characteristics. RESULTS: In total, 450,373 patients were identified (33.5% received 3DCRT, 65.2% received IMRT, and 1.3% received PBRT) with median follow-up of 5.1 years after RT completion and a cumulative follow-up period of 2.54 million person-years. Overall, the incidence of second cancer diagnosis was 1.55 per 100 patient-years. In a comparison between IMRT versus 3DCRT, there was no overall difference in the risk of second cancer (adjusted odds ratio [OR], 1.00; 95% CI, 0.97-1.02; P = .75). By comparison, PBRT had an overall lower risk of second cancer versus IMRT (adjusted OR, 0.31; 95% CI, 0.26-0.36; P < .0001). Results within each tumor type generally were consistent in the pooled analyses and also were maintained in propensity score-matched analyses. CONCLUSIONS: The risk of a second cancer diagnosis was similar after IMRT versus 3DCRT, whereas PBRT was associated with a lower risk of second cancer risk. Future work is warranted to determine the cost-effectiveness of PBRT and to identify the population best suited for this treatment.

Survival after neoadjuvant approaches to gastroesophageal junction cancer.

BACKGROUND: Gastroesophageal junction (GEJ) cancers can be treated with equipoise using neoadjuvant chemoradiation (NACRT) or chemotherapy alone (NAC), but the comparative outcomes are unclear. METHODS: Patients with non-metastatic T2-4 or N1-3 GEJ adenocarcinoma who underwent definitive surgery and NAC or NACRT were selected from the National Cancer Database. The primary outcome was overall survival (OS). Multivariable regression and propensity score analysis were used to adjust for age, comorbidity, and other characteristics. RESULTS: We identified 2435 patients treated with NACRT and 648 patients treated with NAC. OS was not significantly different between NACRT and NAC (51% versus 54% at 3 years, respectively, P = 0.11). Extent of pathological downstaging (complete, partial/mixed, none) after NACRT or NAC was highly prognostic of survival. Patients with no response did equally poorly after either preoperative regimen, and NAC was significantly less likely than NACRT to produce any response (adjusted odds ratio 0.62, P < 0.0001). Rate of adjuvant chemotherapy usage was significantly lower after NACRT than after NAC (12% versus 34%, P < 0.0001). In patients with residual tumor and nodal disease, adjuvant chemotherapy was associated with higher OS after NACRT (adjusted hazard ratio 0.81, P = 0.05), but not after NAC. These results were further validated by propensity score analysis. CONCLUSIONS: NACRT had similar survival to NAC despite superior pathological downstaging. Adjuvant chemotherapy is relatively underused after NACRT and warrants further study as a risk-adapted means to improve survival, especially in patients with larger burden of residual disease.

Clinical impact of the VOLO optimizer on treatment plan quality and clinical treatment efficiency for CyberKnife.

With the recent CyberKnife treatment planning system (TPS) upgrade from Precision 1.0 to Precision 2.0, the new VOLO optimizer was released for plan optimization. The VOLO optimizer sought to overcome some of the limitations seen with the Sequential optimizer from previous TPS versions. The purpose of this study was to investigate the clinical impact of the VOLO optimizer on treatment plan quality and clinical treatment efficiency as compared to the Sequential optimizer. Treatment plan quality was evaluated in four categories of patients: Brain Simple (BS), Brain Complex (BC), Spine Complex (SC), and Prostate (PC). A total of 60 treatment plans were compared using both the Sequential and VOLO optimizers with Iris and MLC collimation with the same clinical constraints. Metrics evaluated included estimated treatment time, monitor units (MUs) delivered, conformity index (CI), and gradient index (GI). Furthermore, the clinical impact of the VOLO optimizer was evaluated through statistical analysis of the patient population treated during the 4 months before (n = 297) and 4 months after (n = 285) VOLO introduction. Significant MU and time reductions were observed for all four categories planned. MU reduction ranged from -14% (BS Iris) to -52% (BC MLC), and time reduction ranged from -11% (BS Iris) to -22% (BC MLC). The statistical analysis of patient population before and after VOLO introduction for patients using 6D Skull tracking with fixed cone, 6D Skull tracking with Iris, and Xsight Spine tracking with Iris were -4.6%, -22.2%, and -17.8% for treatment time reduction, -1.1%, -22.0%, and -28.4% for beam reduction and -3.2%, -21.8%, and -28.1% for MU reduction, respectively. The VOLO optimizer maintains or improves the plan quality while decreases the plan complexity and improves treatment efficiency. We anticipate an increase in patient throughput with the introduction of the VOLO optimizer.

Signet ring cell carcinoma of the Ampulla of Vater: outcomes of patients in the United States.

BACKGROUND: Signet ring cell carcinoma (SRCC) of the ampulla of Vater is poorly understood, with approximately 22 reported cases. Our study sought to create a comprehensive review of cases in the United States. METHODS: We used the Surveillance, Epidemiology, and End Results Program to collect all cases of ampullary adenocarcinoma diagnosed between 2010 and 2015. RESULTS: The age-adjusted incidence rate of SRCC of the ampulla of Vater was 1.2 cases per 10,000,000 persons per year, with 50% more cases in males than females. We identified 3448 cases of adenocarcinoma of the ampulla of Vater, 81 of which were SRCC (2.3%). SRCC tended to present a later stage than other ampullary cancers, with median survival times of 17 vs. 25 months, (p = 0.07). Survival was significantly worse for SRCC when accounting for other clinical features (HR 1.46, p = 0.01). Factors portending worse prognosis in SRCC of the ampulla of Vater were advanced age, late stage and lack of surgical intervention. CONCLUSION: Our study represents the largest study of SRCC of the ampulla of Vater to date. SRCC has a poorer prognosis compared with other ampullary cancers. Optimal treatment regimen is the most important future area of study.

The impact of state parity laws on copayments for and adherence to oral endocrine therapy for breast cancer.

BACKGROUND: Adherence to endocrine therapy for breast cancer is often inadequate, in part because of out-of-pocket costs for medication. Numerous states have enacted parity laws to limit patient cost-sharing for oral anticancer drugs. The objective of this study was to estimate the impact of these laws on patient copayments for and adherence to oral endocrine therapy for breast cancer. METHODS: Administrative health insurance claims data from 2007 to 2014 derived from a US health care database were used to identify female patients aged 18 to 64 years with invasive cancer or ductal carcinoma in situ of the breast who initiated endocrine therapy and were enrolled in fully insured health plans in states that either enacted parity legislation between 2008 and 2013 or had not yet enacted such legislation by 2015. Differences-in-differences analysis was used to compare copayments for and adherence to endocrine therapy during the 1-year period before and after each year of legislation enactment. RESULTS: In total, 6900 individuals who received 7778 unique drug therapy courses were identified. Parity legislation was associated with significant decreases in the 25th percentile of copayments for anastrozole of $4.39 (95% confidence interval [CI], -$4.52 to -$4.26; P < .001) and for exemestane of $3.08 (95% CI, -$4.80 to -$1.35; P < .001). The median copayment for exemestane decreased by $10.25 (95% CI, -$12.61 to -$7.89; P < .001). A higher median monthly copayment was significantly associated with a greater risk of medication nonadherence (adjusted risk ratio, 1.006 per dollar increase; P < .001). CONCLUSIONS: Parity laws had a modest effect on lowering the cost of anastrozole and exemestane, but more focused efforts to limit out-of-pocket costs for endocrine therapy may have a greater impact on medication adherence.