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Background Patients with metastatic cancer referred to radiation oncology have diverse prognoses and there is significant interest in personalizing treatment. We hypothesized that patients selected for higher biologically equivalent doses have improved overall survival. Methods The study population consists of 355 consecutive adult patients with distant metastases treated by a single radiation oncologist from 2014 to 2018. The validated NEAT model was used to prospectively stratify patients into four distinct cohorts. Radiation dose intensity was standardized using the equivalent dose in 2 Gy fractions (EQD2) model with an α/β of 10. Radiation dose intensity on survival was assessed via Cox regression models and propensity score match pairing with Kaplan–Meier analysis. Results The median survival was 9.3 months and the median follow‐up for surviving patients was 18.3 months. The NEAT model cohorts indicated median survivals of 29.5, 11.8, 4.9, and 1.8 months. Patients receiving an EQD2 of ≥40 Gy had a median survival of 16.0 months versus 3.8 months for patients receiving an EQD2 of, Personalized radiotherapy treatment options for patients with metastatic is of significant interest and prompted investigation into higher biological equivalent doses to see if there was increased survival. Higher dose intensity was used for patients with better progresses and was associated with improved survival with metastatic diseases.

To evaluate the association of various gene expression assays with pathologic complete response (pCR) in the setting of neoadjuvant chemotherapy among patients with breast cancer The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with stage I-III breast cancer who underwent neoadjuvant chemotherapy and either 21-gene recurrence score (RS) or 70-gene signature (GS). Logistic multivariable analysis (MVA) was performed to identify variables associated with pCR. A total of 3009 patients met our inclusion criteria. The median follow up was 48.0 months (interquartile range 32.2–66.7 months). On logistic MVA for all patients, those with a high risk from GS (adjusted odds ratio [aOR] 3.23, 95% confidence interval [CI] 1.49–8.13, p = 0.006) or with RS ≥ 31 (aOR 1.99, 95% CI 1.41–2.82, p

Langerhans cell histiocytosis (LCH) is a rare disease, afflicting approximately 4.6 and 1-2 per 1 million children and adults, respectively. While LCH can involve numerous organ systems such as the lung or bone, it is uncommon for the disease to be limited to the skin. Radiotherapy has an established role for osseous lesions. However, the efficacy and dose for nonosseous manifestations of the disease are not well described. In the current case report, we detail a 49-year-old adult male with skin-limited LCH requiring palliative radiotherapy (RT) to numerous sites for pain control. The patient was initially diagnosed and treated with single agent cytarabine for approximately 6 months. Despite treatment, he had little symptomatic response of his cutaneous lesions. We delivered a single dose of 8 Gray (Gy) to 3 separate skin lesions, including the bilateral groin, right popliteal region, and right axillary lesion, which resulted in pain reduction and partial response at four-month follow-up. Subsequently, we decided to treat the left axillary untreated lesion to a higher dose of 24 Gy in 12 fractions. At four-month follow-up, the left axilla RT resulted in complete clinical response and improved pain control compared to the right axilla. Following RT treatments, the patient was found to have a BRAF mutation, and vemurafenib was initiated. Further follow-up with positron emissions tomography demonstrated complete metabolic response in numerous disease areas, including both axillae. Based on this case report’s findings, a higher radiotherapy dose may be more effective for treating cutaneous LCH.

Background Radiation dose to specific cardiac substructures can have a significant on treatment related morbidity and mortality, yet definition of these structures is labor intensive and not standard. Autosegmentation software may potentially address these issues, however it is unclear whether this approach can be broadly applied across different treatment planning conditions. We investigated the feasibility of autosegmentation of the cardiac substructures in four-dimensional (4D) computed tomography (CT), respiratory-gated, non-contrasted imaging. Aim To determine whether autosegmentation can be successfully employed on 4DCT respiratory-gated, non-contrasted imaging. Methods We included patients who underwent stereotactic body radiation therapy for inoperable, early-stage non-small cell lung cancer from 2007 to 2019. All patients were simulated via 4DCT imaging with respiratory gating without intravenous contrast. Generated structure quality was evaluated by degree of required manual edits and volume discrepancy between the autocontoured structures and its edited sister structure. Results Initial 17-structure cardiac atlas was generated with 20 patients followed by three successive iterations of 10 patients using MIM software. The great vessels and heart chambers were reliably autosegmented with most edits considered minor. In contrast, coronary arteries either failed to be autosegmented or the generated structures required major alterations necessitating deletion and manual definition. Similarly, the generated mitral and tricuspid valves were poor whereas the aortic and pulmonary valves required at least minor and moderate changes respectively. For the majority of subsites, the additional samples did not appear to substantially impact the quality of generated structures. Volumetric analysis between autosegmented and its manually edited sister structure yielded comparable findings to the physician-based assessment of structure quality. Conclusion The use of MIM software with 30-sample subject library was found to be useful in delineating many of the heart substructures with acceptable clinical accuracy on respiratory-gated 4DCT imaging. Small volume structures, such as the coronary arteries were poorly autosegmented and require manual definition.

Among patients with early-stage breast cancer and a high 21-gene recurrence score (RS) ≥ 26, it remains unclear on whether those with RS 26-30 would benefit from chemotherapy with a comparable magnitude as those with RS 30. In addition, RS 30 as an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) compared to RS 26-30 also remains unclear. The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed between 2010 and 2013 with hormone receptor-positive, HER2-negative, and T1-2N0 breast cancer with a RS ≥ 26. Primary end points were OS and BCSS, evaluated by using Kaplan-Meier method, log-rank test, and Cox multivariable analysis. Subgroups of RS 26-30 and RS 30 were examined using propensity score matching to address selection bias. Among 5054 patients who met the inclusion criteria, adjuvant chemotherapy was associated with improved OS (HR 0.66, 95% CI 0.53-0.83, P .001) and BCSS (HR 0.61, 95% CI 0.45-0.83, P = .001). In the subgroup of 943 matched pairs of patients with RS 26-30, the addition of chemotherapy remained statistically significant (OS: HR 0.52, 95% CI 0.34-0.79, P = .003; BCSS: HR 0.42, 95% CI 0.22-0.81, P = .009). Among 1194 matched pairs who underwent adjuvant chemotherapy, those with RS 30 had worse outcomes than others with RS 26-30 (OS: HR 1.68, 95% CI 1.17-2.42, P = .005; BCSS: HR 1.92, 95% CI 1.17-3.15, P = .01). Our study builds on prior literature using a population-based database to suggest the association of adjuvant chemotherapy with improved survival among those with RS 26-30 and worse mortality associated with RS 30 compared to RS 26-30.

BACKGROUND β-blocker use has been associated with improved outcomes in a number of different malignancies; however, the impact of β-blockade in esophageal cancer is not been well characterized. We compared the outcomes of esophageal cancer patients based on β-blocker usage. METHODS The charts of all 418 patients treated with radiation for esophageal cancer at our institution from April 2010 to October 2018 were analyzed. Patients who underwent treatment with palliative intent or did not finish treatment were excluded. β-blocker use was determined from the medication list at time of pretreatment consultation. RESULTS There were 291 esophageal cancer patients who received neoadjuvant/definitive chemoradiation therapy. The median follow-up for the cohort was 22.5 months (interquartile range: 9.6 to 41.0 mo). Within the cohort, 27.8% (n=81) of patients were taking β-blockers at the time of treatment. Those taking β-blockers had significantly improved distant control (22.2% vs. 37.9%; P=0.035). Concomitant β-blocker use was significantly associated with improved progression-free survival (P

Prognostication for cancer patients is integral for patient counseling and treatment planning, yet providing accurate prediction can be challenging using existing patient-specific clinical indicators and host factors. In this work, we evaluated common machine learning models in predicting head and neck squamous cell carcinoma (HNSCC) patients’ overall survival based on demographic, clinical features and host factors. We found random survival forest had best performance among the models evaluated, which achieved a C-index of 0.729 and AUROC of 0.792 in predicting two-year overall survival. In addition, we verified that host factors are independently predictive of HNSCC overall survival, which improved the C-index by a margin of 0.026 and the AUROC by 0.034. Due to the strong correlation among host factors, we showed that proper dimension reduction is an important step before their incorporation into the machine learning models, which provides a host factor score reflecting the patients’ nutrition and inflammation status. The score by itself showed excellent discriminating capacity with the high-risk group having a hazard ratio of 3.76 (1.93–7.32, p &lt, 0.0001) over the low-risk group. The hazard ratios were further improved to 7.41 (3.66–14.98, p &lt, 0.0001) by the random survival forest model after including demographic and clinical features.

Objective:Patients undergoing prostate radiation therapy were observed to have elevated blood pressures in clinic. Therefore, we sought to further characterise this phenomenon.Methods:The charts of 76 patients who received radiotherapy for prostate cancer between 2014 and 2017 were examined. Blood pressure (BP) readings were obtained at initial consultation, on treatment visits, and subsequent follow-up appointments. To describe this effect, we defined radiation-associated hypertension (RAH) as an increase ≥15 mmHg systolic BP, 10 mmHg diastolic BP, or 5 mmHg mean arterial pressure.Results:Within this cohort, 36 patients developed RAH, with 75% developing RAH while on treatment, and 25% developing RAH at post-treatment visits. Two-thirds of patients remained hypertensive during post-treatment visits, and 27% were prescribed additional anti-hypertensives. There was no association between neoadjuvant/concurrent androgen deprivation therapy and RAH.Conclusion:A significant number of patients undergoing prostate radiotherapy developed RAH, necessitating additional medication in some.

The association between HRQOL metrics and survival has not been studied in early stage non-small-cell lung cancer (NSCLC) patients undergoing SBRT. The cohort was derived via a post-hoc analysis of a prospective randomized clinical trial examining definitive SBRT for peripheral, early-stage NSCLC with a single or multi-fraction regimen. Patients completed HRQOL questionnaires prior to and 3 months after treatment. Using principal component analysis (PCA), changes in each HRQOL scale following treatment were reduced to two eigenvectors, PC1 and PC2. Cox regression was employed to analyze associations with survival-based endpoints. A total of 70 patients (median age 75.6 years, median follow-up 41.1 months) were studied. HRQOL and symptom comparisons at baseline and 3 months were vastly unchanged except for improved coughing (p = 0.02) and pain in the chest at 3 months (p = 0.033). PC1 and PC2 explained 21% and 9% of variance, respectively. When adjusting for covariates, PC1 was significantly correlated with progression-free (PFS) (HR = 0.78, 95% CI 0.67–0.92, p = 0.003) and overall survival (OS) (HR = 0.76, 95% CI 0.46, p = 0.041). Changes in global health status, functional HRQOL performance, and/or symptom burden as described by PC1 values are significantly associated with PFS and OS. The PC1 quartile may facilitate the identification of at-risk patients for additional interventions.

Simple Summary Quality of life (QOL) is an important patient reported outcome that effects both care and life outside of treatment. There is a shortage of nontaxing ways to determine which patients may need enhanced care over the course of their therapy and beyond to help avoid long-term declines in QOL. Therefore, we investigated whether myosteatosis as determined through existing diagnostic imaging could be used to predict QOL trajectories. In this study, patients with pretreatment myosteatosis were more likely to have lower physical and global QOL scores than patients with normal muscle density. In conclusion, myosteatosis may be a way of determining patients in need of extra assistance over the course of treatment and afterwards. Abstract Head and neck cancer (HNC) treatment-related morbidity can be detrimental to quality of life (QOL). Myosteatosis is associated with poor QOL in multiple cancers. If predictive of poor QOL trajectories, myosteatosis would be a tool for clinicians to determine which patients may require additional support during treatment. The purpose of this study was to determine if pretreatment myosteatosis is associated with a poor QOL trajectory following treatment completion. Methods: In a retrospective cohort design, myosteatosis was determined from pretreatment CT scans. Both physical and global QOL score was assessed through patient interview on follow-up appointment. Demographic, cancer-specific, and social covariates were collected, reported, and considered as potential confounders. Results: The population of 163 patients was mostly male (82.2%) and white (91.4%) with oropharyngeal cancer (55.8%). Males with myosteatosis had a physical QOL score 46.84 points lower at one-year following treatment completion (p = 0.01) than those with normal muscle density (p = 0.01). Males with myosteatosis averaged 57.57 points lower at one-year post-treatment (p = 0.01) in global QOL scores. Conclusions: Over one year following completion of treatment, patients with myosteatosis reported worse physical and global QOL scores than patients with normal muscle density.

Oral mucositis (OM) can be a significant problem for patients undergoing radiation or chemoradiation for head and neck cancer. In modern clinical trials, grade 3-4 OM can be seen in over 40% of patients and can cause a significant impact on their quality of life (QOL). Despite this fact, strategies for the prevention and treatment of OM vary widely, with options including both lifestyle modifications and pharmaceuticals. Here we evaluate and summarize the current clinical interventions for the management of radiation-induced OM. The majority of the current evidence focuses on reducing OM related pain. These agents are detailed over multiple clinical trials including treatment modalities such as: GC4419, doxepin mouthwash, diphenhydramine-lidocaine-antacid (DLA) mouthwash, gabapentin, and methadone. While several strategies have been employed to prevent radiation-induced OM, there is currently no strong evidence for the routine use of these agents in the clinic. After summarization of these treatments, we offer practical guidance for the treatment of OM in the clinic. We recommend a multiagent approach of pharmacological and non-pharmacological treatments including oral rinses, home humidification, escalating doses of gabapentin, doxepin or DLA mouthwash, over the counter analgesics, and lastly methadone. These interventions are tailored to address the expected increase of severity of symptoms during the course of head and neck radiotherapy.

Simple Summary The optimal way to treat central (CLT) and ultracentral (UCLT) lung tumors with curative radiation is unclear. We evaluated 83 patients with CLT and UCLT who underwent a curative radiotherapy technique called stereotactic body radiation therapy (SBRT). On statistical analysis, patients with UCLT had worse overall survival. Using a cohort of patients matched for relevant variables such as gender and performance status, we evaluated radiation doses to critical central structures such as the airway and heart. In this group, patients with UCLT were more likely to exceed dose constraints as compared CLT, particularly constraints regarding the airway. Additionally, patients had worse non-cancer associated survival when radiation doses were higher than 18 Gy to 4cc’s of either the trachea or proximal bronchial tree. Based on these findings, patients with UCLT have worse outcomes which could be secondary to higher radiation doses to the trachea and proximal bronchial tree. Abstract The preferred radiotherapeutic approach for central (CLT) and ultracentral (UCLT) lung tumors is unclear. We assessed the toxicity and outcomes of patients with CLT and UCLT who underwent definitive five-fraction stereotactic body radiation therapy (SBRT). We reviewed the charts of patients with either CLT or UCLT managed with SBRT from June 2010–April 2019. CLT were defined as gross tumor volume (GTV) within 2 cm of either the proximal bronchial tree, trachea, mediastinum, aorta, or spinal cord. UCLT were defined as GTV abutting any of these structures. Propensity score matching was performed for gender, performance status, and history of prior lung cancer. Within this cohort of 83 patients, 43 (51.8%) patients had UCLT. The median patient age was 73.1 years with a median follow up of 29.9 months. The two most common dose fractionation schemes were 5000 cGy (44.6%) and 5500 cGy (42.2%) in five fractions. Multivariate analysis revealed UCLT to be associated with worse overall survival (OS) (HR = 1.9, p = 0.02) but not time to progression (TTP). Using propensity score match pairing, UCLT correlated with reduced non-cancer associated survival (p = 0.049) and OS (p = 0.03), but not TTP. Within the matched cohort, dosimetric study found exceeding a D4cc of 18 Gy to either the proximal bronchus (HR = 3.9, p = 0.007) or trachea (HR = 4.0, p = 0.02) was correlated with worse non-cancer associated survival. In patients undergoing five fraction SBRT, UCLT location was associated with worse non-cancer associated survival and OS, which could be secondary to excessive D4cc dose to the proximal airways.

Simple Summary Financial toxicity (FT) can be devastating to cancer patients, and solutions are urgently needed. We investigated how providing financial counseling (FC) for head and neck cancer (HNC) patients undergoing radiation therapy impacted patients’ financial difficulties at the end of treatment. Beginning in July 2018, a dedicated financial counselor was provided, and all eligible patients received FC. Via a survey, patients who did not have FC reported a significant increase in financial difficulty at the end of treatment however those who had received FC did not report such an increase. Furthermore, in a statistical model FC was associated with significantly lower financial difficulty scores. Based on the findings, the employment of a financial counselor may be a viable, hospital-based approach to begin to address FT in HNC. Abstract Background: Financial toxicity (FT) can be devastating to cancer patients, and solutions are urgently needed. We investigated the impact of financial counseling (FC) on FT in head and neck cancer (HNC) patients. Methods: Via a single-institution database, we reviewed the charts of HNC patients who underwent definitive or post-operative radiotherapy, from October 2013 to December 2020. Of these patients, 387 had provided baseline and post-treatment information regarding financial difficulty. In July 2018, a dedicated financial counselor was provided for radiation therapy patients and we subsequently examined the impact of FC on financial difficulty scores. Results: Following the hiring of a dedicated financial counselor, there was a significant increase in the proportion of patients receiving FC (5.3% vs. 62.7%, p < 0.0001). Compared with baseline scores, patients who did not undergo FC had a significant increase in reported financial difficulty at the end of treatment (p = 0.002). On the other hand, there was no difference in pre- and post-treatment scores in patients who had received FC (p = 0.588). After adjusting for gender and nodal status with a multiple linear regression model, FC was significantly associated with change in financial difficulty (β = −0.204 ± 0.096, p = 0.035). On average, patients who received FC had a 0.2 units lower change in financial difficulty score as compared with those with the same gender and nodal stage but without FC. Conclusions: Providing a dedicated financial counselor significantly increased the proportion of HNC receiving FC, resulting in the stabilization of financial difficulty scores post-treatment. Based on a multiple linear regression model, FC was independently associated with reduced financial difficulty. The employment of a financial counselor may be a viable, hospital-based approach to begin to address FT in HNC.

Simple Summary Quality of life (QoL) scores and frailty status are becoming increasingly important criterion with implications on both how patients are treated and survival in head and neck cancer (HNC). Despite this, physicians lack tools to identify patients who are at risk of suffering declines in QoL and becoming frail following treatment. Therefore, we investigated whether functional decline, as measured by a series of physical tests called the Short Physical Performance Battery (SPPB), correlated with a reduction in QoL and increased risk of frailty. In the current study, patients who experienced a decline in SPPB scores were significantly more likely to have changes in physical functioning QoL measures as well as transition to frail status following treatment. In conclusion, the SPPB may be a useful tool to identify patients who may benefit from additional rehabilitation in future studies. Abstract Patient-reported quality of life (QoL) metrics, frailty status, and physical functioning are emerging concepts in head and neck cancer (HNC) with implications on both treatment decision-making and prognosis. The impact of treatment-related functional decline on QoL and frailty has not been well-characterized in HNC and was the focus of this investigation. Methods: Patients who underwent radiation therapy for HNC from 2018 to 2020 were evaluated as a prospective observational cohort. Functional decline, QoL, and the frailty phenotype were measured via the Short Physical Performance Battery (SPPB), European Organization for Research and Treatment of Cancer (EORTC) qlq-C30, and Fried Frailty index, respectively. Results: A total of 106 HNC patients were included, 75 of which received concurrent chemoradiation therapy (CCRT) and 31 received radiation alone, both with and without surgery. There was a decrease in SPPB overall (p < 0.001) from the beginning to the end of treatment in the CCRT group but not the radiation group (p = 0.43). Change in overall SPPB points following treatment correlated with the decline in physical QoL for both groups (p < 0.05) as well as transition frail status in the CCRT group (p < 0.001) with a trend in the radiation group (p = 0.08). Conclusions: Change in SPPB correlates with QoL and transition to frailty status in patients undergoing definitive CCRT for HNC with similar trends in those receiving radiation alone. Decline in SPPB could potentially be useful in identification of those who may benefit from rehabilitation in future studies.

Simple Summary Following completion of chemotherapy and radiation for the treatment of head and neck cancer, a PET/CT scan is typically obtained 3 months later to assess how well the patient responded to treatment. The results of this PET/CT are often difficult to interpret because radiation can cause inflammation around the area being treated that can take months to resolve. We looked at 57 patients who had a repeat PET/CT scan performed after initial post-treatment imaging was unclear to examine whether this was helpful in determining whether these patients require further testing. Among this group, 48% of patients converted to having a complete response to treatment and none went on to develop treatment failure. Based on our findings, repeat PET/CT imaging can provide valuable information for head and neck cancer patients that can reduce the incidence of unnecessary biopsies and surgeries. Abstract Despite waiting 13 weeks to perform a PET/CT scan after completion of chemoradiation for head and neck squamous cell carcinoma (HNSCC), equivocal findings are often found that make assessing treatment response difficult. This retrospective study examines the utility of a repeat PET/CT scan in HNSCC patients following an incomplete response on initial post-treatment imaging. For this cohort of 350 patients, initial PET/CT was performed 13 weeks after completion of treatment. For select patients with an incomplete response, repeat PET/CT was performed a median of 91 days later. Primary endpoints were conversion rate to complete response (CR) and the predictive values of repeat PET/CT imaging. Of 179 patients who did not have an initial complete response, 57 (32%) received a repeat PET/CT scan. Among these patients, 26 of 57 (48%) had a CR on repeat PET/CT. In patients with CR conversion, there were no cases of disease relapse. The sensitivity, specificity, PPV, and NPV for the repeat PET/CT for locoregional disease were 100%, 59%, 42%, and 100%. Repeat PET/CT in HNSCC patients with an incomplete post-treatment scan can be valuable in obtaining diagnostic clarity. This can reduce the incidence of unnecessary biopsies and neck dissections.

Simple Summary Health-related quality of life (HRQOL) surveys describe the patient experience of disease and treatment. The relationship between post-treatment recovery of HRQOL and outcome in head and neck cancer is not well characterized. Impaired recovery of numerous individual components of HRQOL were associated with increased mortality. To obtain a better understanding how HRQOL (as a whole) impacts survival, we utilized a statistical technique called principal component analysis (PCA). PCA generated a total score of several HRQOL domains, named principal component 1 (PC1), to more accurately describe the cumulative impact of poor HRQOL recovery on outcome. PC1 was associated with survival and may be a useful tool in future studies to identify at-risk patients. Abstract Background: Health-related quality of life (HRQOL) metrics can be associated with survival in head and neck cancer (HNC); however, the impact of HRQOL recovery and the relevant HRQOL domains regarding outcome are unclear. Methods: Using a single-institution database, we retrospectively reviewed HNC patients treated with definitive or postoperative radiation therapy between 2013 and 2018. The recovery of individual HRQOL domains were determined by the ratio of the post-treatment to baseline scores. Univariate and Multivariate Cox regression were used to analyze survival outcomes. Principal component analysis was used to adjust for multicollinearity of HRQOL domains. Results: In 218 HNC patients who received radiation therapy, median follow-up was 24.8 months (interquartile range (IQR) 14.5–32.0). Principal component analysis evaluating the recovery of HRQOL domains revealed two independent principal components (PC), PC1 and PC2. PC1, which received contributions from the functional domains; physical (PF), role (RF), emotional (EF), cognitive (CF), and global health status (GQOL) was significantly associated with disease-free (HR = 0.77, 95% CI 0.61–0.98, p = 0.034) and overall survival (HR = 0.76, 95% CI 0.65–0.91, p = 0.004) on multivariate analysis and PC2, had no correlation with outcome and was mainly represented by social functioning. Unplanned hospitalization was significantly associated with lower PC1 scores (β = −0.997, Std. Error = 0.244, p < 0.001). Conclusion: Our study provides evidence that post-treatment recovery of HRQOL domains were associated with overall survival (OS) in HNC. PC1 is an attractive clinical tool to assess the recovery across multiple different HRQOL and the relationship with survival. Future prospective studies may identify patients who could benefit from additional rehabilitation based on PC1 score.

PURPOSE/OBJECTIVE(S) Several prospective trials demonstrated the feasibility of the omission of adjuvant radiation therapy (RT) among elderly breast cancer patients without worsening overall mortality. However, 50-70% of patients could not finish the full course of adjuvant ET, and select elderly patients may be at risk for undertreatment and tumor recurrences. This study compares the survival outcome of various adjuvant therapies in elderly patients with breast cancer. MATERIALS/METHODS The National Cancer Database (NCDB) was queried for female patients above 65 years old, diagnosed between 2010 and 2015 with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-2N0 (tumor size up to 3 cm) breast cancer who underwent BCS followed by either adjuvant RT, ET, or both. Primary endpoint was overall survival (OS), evaluated by Kaplan-Meier method, log-rank test, and Cox multivariable analysis. Propensity score matching was used to address selection bias. RESULTS A total of 16494 patients with a median age of 69 (interquartile range [IQR] 67-73) were analyzed, including 814, 1425, and 14255 patients treated with RT, ET, or both, respectively. On Cox multivariable analysis, ET alone was not associated with improved survival outcome (hazards ratio [HR] 1.00, 95% confidence interval [CI] 0.73-1.38, P = 1.00) compared to RT alone. However, RT combined with ET was associated with improved OS (HR 0.59, 95% CI 0.45-0.76, P < 0.001) compared to RT alone. When propensity score matching was performed, 424 and 683 pairs were matched for RT vs ET alone and RT vs RT and ET. All patient and tumor characteristics were well balanced. There was no difference in OS between RT and ET alone (HR 0.99, 95% CI 0.60-1.65, P = 0.97), while RT combined with ET was associated with improved OS (HR 0.54, 95% CI 0.34-0.86, P = 0.009). CONCLUSION RT alone may be considered as an alternative option in elderly patients who decline or may not tolerate ET, while RT combined with ET may be preferred for select elderly patients.

Simple Summary Those with a history of colorectal cancer benefit from aspirin following completion of treatment, however, it is believed that this benefit is restricted to patients who have tumors with certain mutations. It is not known whether taking aspirin during active treatment helps patients or whether it depends on tumor genetics in this setting. We investigated 147 patients who underwent chemoradiation for rectal cancer at our institution, including 42 who were taking aspirin at the time of chemoradiation. Concurrent aspirin use was associated with significantly improved tumor control and survival. Genetic analysis of the tumor did not indicate that these benefits were restricted to certain molecular conditions. Interestingly, aspirin was associated with more advantageous immune response in tumor specimens. Based on these findings, the addition of aspirin to chemoradiation should be considered for rectal cancer patients, independent of molecular conditions. Abstract Background: The benefit of aspirin in rectal cancer during chemoradiation therapy (CRT) and the factors affecting its efficacy are not well characterized. We compared the outcomes of rectal patients undergoing neoadjuvant CRT based on aspirin use. Methods: Patients undergoing CRT for rectal cancer from 2010 to 2018 were evaluated. Aspirin use was determined by medication list prior to treatment. RNA sequencing and subsequent gene set enrichment analysis was performed on surgically resected specimens. Results: 147 patients underwent neoadjuvant CRT with a median follow-up of 38.2 months. Forty-two patients were taking aspirin prior to CRT. Aspirin users had significantly less local and distant progression, and improved progression-free and overall survival. On RNA-sequencing, neither PI3KCA nor KRAS mutational status were associated with the benefit of aspirin use or tumor downstaging. PTGS2/COX2 expression trended lower in aspirin users, but not with tumor response. Aspirin use was associated with increases of M1 macrophages, plasma cells, CD8+ T cells, and reduction of M2 macrophages in the resected tumor. Conclusions: Concurrent aspirin use during neoadjuvant CRT was associated with improved local and distant tumor control leading to significantly improved survival. Neither mutations in KRAS or PI3CKA, nor the levels of COX-2 expression at the time of resection of the residual tumor were predictive of these aspirin benefits.

BACKGROUND Despite occurring commonly, the prognoses of second early-stage non-small cell lung cancers (NSCLC) are not well known. METHODS The authors retrospectively reviewed the charts of inoperable patients who underwent thoracic stereotactic body radiation therapy (SBRT) from February 2007 to April 2019. Those with previous small cell lung cancers or SBRT treatments for tumors other than NSCLC were excluded. Multivariate Cox regression and a matched pair cohort analyses evaluated the prognoses of patients undergoing definitive SBRT for a new second primary. RESULTS Of 438 patients who underwent definitive SBRT for NSCLC, 84 had previously treated NSCLC. Univariate log-rank tests identified gender, Karnofksy performance status (KPS), prior lung cancer, anticoagulation use, and history of heart disease to correlate with overall survival (OS) (P

This cohort study compares overall survival among patients with nonmetastatic, resectable retroperitoneal sarcoma treated with surgical treatment alone vs surgical treatment and chemotherapy or radiation.

This cohort study investigates the association between nonsteroidal anti-inflammatory drug (NSAID) use and survival in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy (CRT) at a single institution between 2005 and 2017., Key Points Question Is nonsteroidal anti-inflammatory drug (NSAID) use associated with a survival advantage in patients with head and neck squamous cell carcinoma who are treated with definitive chemoradiation therapy? Findings In this cohort study of 460 patients, NSAID use was associated with significantly better overall survival at 5 years compared with no use of concurrent NSAIDs. Meaning These findings suggest there may be an overall survival advantage for patients with head and neck squamous cell carcinoma who take NSAIDs during chemoradiation., Importance Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are commonly prescribed medications with anti-inflammatory and antiplatelet properties used long term to decrease the risk of cardiovascular events. A recent study showed that aspirin was associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) who were treated with surgery. Objective To examine whether use of NSAIDs during definitive chemoradiation therapy (CRT) was associated with improved outcomes in patients with HNSCC. Design, Setting, and Participants This cohort study analyzed patients with HNSCC who were treated with CRT at a single institution between January 1, 2005, and August 1, 2017. Patient and tumor characteristics included age, race/ethnicity, smoking status, alcohol use, comorbidities (respiratory, cardiovascular, immune, renal, endocrine), disease stage, human papillomavirus status, and treatment duration. Data were analyzed from May 1, 2019, to March 17, 2020. Exposures Patients were dichotomized by NSAID use during treatment. Main Outcomes and Measures The association of NSAID use with patterns of failure, disease-specific survival (DSS), and overall survival (OS) was examined using multivariate Cox proportional hazard regression models. Survival estimates for OS and DSS were generated using Kaplan-Meier survival curves. Results A total of 460 patients (median [interquartile range] age, 60 [53.9-65.6] years; 377 [82.0%] men) were included in the analysis. Among these patients, 201 (43.7%) were taking NSAIDs during treatment. On univariate analysis, NSAID use (hazard ratio [HR], 0.63; 95% CI, 0.43-0.92; P = .02) was associated with better OS. On Cox regression analysis, after backward selection adjustment for potentially confounding factors (age, smoking status, primary tumor site, human papillomavirus status, diabetes, stroke, hyperlipidemia), NSAID use remained significantly associated with better OS (HR, 0.59; 95% CI, 0.38-0.90; P = .02). NSAID use was associated with significantly better OS at 5 years compared with patients who did not take concurrent NSAIDs (63.6% [56 of 88 patients]; 95% CI, 58%-73% vs 56.1% [83 of 148 patients]; 95% CI, 50%-63%; P = .03). NSAID use was not associated with better DSS in univariate (HR, 0.82; 95% CI, 0.48-1.41; P = .47) or multivariate (HR, 0.98; 95% CI, 0.57-1.70; P = .44) analysis. NSAID use was not associated with better response to treatment (HR, 1.44; 95% CI, 0.91-2.27; P = .12) or distant failure (HR, 1.12; 95% CI, 0.68-1.84; P = .65). Change in local control with NSAID use was not statistically significant (HR, 0.59; 95% CI, 0.31-1.10; P = .10). Conclusions and Relevance This cohort study suggests a possible OS advantage for patients taking NSAIDs during chemoradiation for HNSCC. Further studies examining this association are warranted.

Purpose/Objective(s) Conventional prophylaxis for heterotopic ossification (HO) of the hip with radiotherapy (RT) includes treatment of the prosthesis, adductor, and abductor compartments. To limit RT effects on neovascularization and healing after surgery, we routinely used a limited-field RT (LF-RT), which only includes the affected compartment guided by pre-operative imaging. This study aims to examine whether LF-RT was as effective in preventing local recurrence as CF-RT. Materials/Methods We retrospectively reviewed the charts of 85 consecutive patients who underwent post-operative RT for HO from March 2005 to June 2019. Patients treated to non-hip sites or without radiographic follow-up were excluded. RT fields were reviewed to determine whether they fall under CF-RT defined as inclusion of the prosthesis, adductor, and abductor compartments or LF-RT which was defined as the adductor compartment alone. Results A total of 48 patients were eligible. Most patients were male (60.4%), with a median age of 65 years (interquartile range (IQR) 60-75 years), and a median follow-up of 23.8 months (IQR 12.6-53.1 months). Most patients received 7 Gray (81.3%), with the most common technique being 2-dimensional RT (70.8 %). Thirty-six patients (75%) received LF-RT to the abductor compartment, whereas twelve patients (25%) received CF-RT. There was no significant difference in local recurrence between LF-RT (0%) and CF-RT (8.3%) (P = 0.4). No ipsilateral re-treatment was required in LF-RT patients compared to one CF-RT patient (8.3 %). The single recurrence in the CF-RT group was retreated with CF-RT. There were no recorded acute or late adverse events related to either field. No patient in either group required non-radiation secondary interventions such as hip injections or surgical revision for HO. Conclusion Within this limited cohort, LF-RT was similarly efficacious as CF-RT in prophylaxis for HO of the hip with no added toxicity. Future centers that are interested in adopting LF-RT should routinely acquire pre-operative images to aid in the creation of treatment volumes.

PURPOSE/OBJECTIVE(S) Central (CLT) and ultracentral (UCLT) lung tumors can be at higher risk for treatment related mortality following stereotactic body radiation therapy (SBRT) and the preferred dose and fractionation is unclear. We assessed the toxicity and outcomes of patients with CLT and UCLT who underwent definitive five-fraction SBRT. MATERIALS/METHODS We reviewed the charts of patients with either CLT or UCLT managed with SBRT from June 2010-April 2019. CLT were defined as gross tumor volume within 2 cm of either the proximal bronchial tree, trachea, mediastinum, aorta, or spinal cord. UCLT were defined as GTV abutting any of these structures. Toxicity was graded by the Common Terminology Criteria for Adverse Events version 5.0. Propensity score matching was performed for gender, performance status, and history of prior lung cancer. Survival outcomes evaluated by Cox regression and Kaplan-Meier estimation. RESULTS Within this cohort of 83 patients, the median age was 73.1 years with a median follow up of 29.9 months. All patients underwent 5 fraction SBRT, with dose range of 50-60 Gy. Most patients had T1 tumors (68.7%) and 43 (51.8%) were considered UCLT. In 20 (50%) patients with CLT, the proximal bronchial tree was the closest central structure while the aorta was the closest structure in 16 (37.2%) of UCLT patients. Grade 2+ toxicity was similar between the two groups, 11 (27.5%) for CLT and 13 (30.2%) (P = 0.78) for UCLT patients. Furthermore, there was no difference in grade 3 toxicity with 3 (7.5%) CLT and 4 (9.3%) UCLT patients (P = 0.77) and no observed grade 4+ events. There was no difference in crude local failure (5% vs 7.0%) (P = 0.34) or recurrence rates (22.5% vs 9.3) (P = 0.09). Multivariate analysis adjusting for gender, performance status, prior lung cancer, history of diabetes, history of heart disease, and prescription volume revealed UCLT to be associated with worse overall survival (OS) (P = 0.02) but not freedom from progression (FFP). Using propensity score match pairing, 29 match pairs were generated finding UCLT to correlate with reduced non-cancer related survival (NC-OS) and OS, but not FFP. CONCLUSION Definitive 5 fraction SBRT yielded similar toxicity profiles for CLT and UCLT. Despite no difference in FFP, UCLT were associated with worse (NC-OS) and OS.

PURPOSE/OBJECTIVE(S) Optimal preoperative therapy regimen in the treatment of resectable retroperitoneal sarcoma remains unclear. This study compares the impact of preoperative radiation, chemoradiation, and chemotherapy on overall survival. MATERIALS/METHODS The National Cancer Database (NCDB) was queried for patients diagnosed between 2006 and 2015 with non-metastatic, resectable RPS with follow up through 2017, treated with preoperative therapies followed by surgery. Primary endpoint was overall survival (OS), evaluated by Kaplan-Meier method, log-rank test, and Cox multivariable analysis. Propensity score matching was used to address selection bias. RESULTS A total of 1253 patients met the inclusion criteria, with 210 patients (17%) receiving chemoradiation, 850 patients (68%) receiving radiation, and 193 patients (15%) receiving chemotherapy. On Cox multivariable analysis compared to preoperative chemoradiation, preoperative radiation was not associated with improved OS (hazards ratio [HR] 0.98, 95% CI 0.76-1.25, P = 0.84), while preoperative chemotherapy was associated with worse OS (HR 1.64, 95% confidence interval [CI] 1.24-2.18, P < 0.001). Recent years of diagnosis (HR 1.30, 95% CI 1.08-1.58, P = 0.007), elderly age (HR 1.32, 95% CI 1.10-1.59, P = 0.003), male gender (HR 1.20, 95% CI 1.00-1.43, P = 0.047), lower income (HR 1.19, 95% CI 1.00-1.43, P = 0.049), poorly differentiated (HR 2.53, 95% CI 1.84-3.48, P < 0.001) or other tumor grade (HR 2.44, 95% CI 1.75-3.40, P < 0.001), and positive surgical margin (HR 1.37, 95% CI 1.12-1.68, P = 0.002) were associated with worse OS. Similar findings were observed in 199 and 128 matched pairs for preoperative radiation and chemotherapy respectively when compared to preoperative chemoradiation. CONCLUSION Our study suggested an OS benefit in using preoperative chemoradiation compared to chemotherapy alone, but OS outcomes were comparable between preoperative chemoradiation and radiation alone. Further studies are warranted to optimize preoperative therapies.

Background: Limited treatment options are available for oral mucositis, a common, debilitating complication of cancer therapy. We examined the association between daily delivery time of radiotherapy and the severity of oral mucositis in patients with head and neck cancer. Methods: We used electronic medical records of 190 patients with head and neck squamous cell carcinoma who completed radiotherapy, with or without concurrent chemotherapy, at Roswell Park Comprehensive Cancer Center (Buffalo, NY) between 2015 and 2017. Throughout a 7-week treatment course, patient mouth and throat soreness (MTS) was self-reported weekly using a validated oral mucositis questionnaire, with responses 0 (no) to 4 (extreme). Average treatment times from day 1 until the day before each mucositis survey were categorized into seven groups. Multivariable-adjusted marginal average scores (LSmeans) were estimated for the repeated- and maximum-MTS, using a linear-mixed model and generalized-linear model, respectively. Results: Radiation treatment time was significantly associated with oral mucositis severity using both repeated-MTS (n = 1,156; P = 0.02) and maximum-MTS (n = 190; P = 0.04), with consistent patterns. The severity was lowest for patients treated during 8:30 to Conclusions: We report a significant association between radiation treatment time and oral mucositis severity in patients with head and neck cancer. Impact: Although additional studies are needed, these data suggest a potential simple treatment time solution to limit severity of oral mucositis during radiotherapy without increasing cost.

Objectives Positron-emission tomography (PET) has improved identification of the primary tumor as well as occult nodal burden in cancer of the head and neck. Nevertheless, there are still patients where the primary tumor cannot be located. In these situations, the standard of care is comprehensive head and neck radiation therapy however it is unclear whether this is necessary. This study examines the effects of radiation treatment volume on outcomes among using data from two cancer centers in unknown primary carcinoma of the head and neck. Methods Patients received unilateral (n = 34), or bilateral radiation (n = 28). Patient factors such as age, gender, smoking history, and patterns of failure were compared using Mann Whitney U and Chi Square. Overall survival (OS) and disease free survival (DFS) trends were estimated using Kaplan-Meier survival curves. Effect of treatment volume on survival was examined using multivariate cox proportional hazard regression model. Results No significant differences were observed in the frequency of local (p = 0.32), regional (p = 0.50), or distant (p = 0.76) failures between unilateral and bilateral radiation therapy. By Kaplan-Meier estimates, OS (3-year OS bilateral = 71.67%, unilateral = 77.90%, p = 0.50) and DFS (3-year DFS bilateral = 77.92%, unilateral = 69.43%, p = 0.63) were similar between the two treatment approaches. Lastly, multivariate analysis did not demonstrate any significant differences in outcome by treatment volumes (OS: HR = 0.74, 95% CI: 0.31, 1.81, p = 0.51; DFS: HR: 0.68, 95% CI: 0.24, 1.93, p = 0.47). Conclusions Unilateral radiation therapy compared with bilateral produced similar survival.

575 Background: Given improvements in systemic therapy, pathologic complete response (pCR) rates following neoadjuvant chemotherapy were over 60% in breast cancer patients in recent clinical trials, especially in human epidermal growth factor receptor 2 (HER2)-positive and triple negative cases. While racial minority groups were associated with worse survival outcomes despite receiving standard of care in prospective studies, they were under-represented in clinical trials. To address this knowledge gap, we performed an observational cohort study to evaluate pCR and survival outcomes stratified by racial and ethnic groups. Methods: The National Cancer Database (NCDB) was queried for female patients with stage I-III breast cancer diagnosed between 2010 and 2017 treated with neoadjuvant chemotherapy followed by surgery. Cochran-Armitage test was used to analyze the trend of pCR over time. Logistic multivariable analysis (MVA) was used to identify variables associated with pCR defined as ypT0/isN0. Cox MVA was used to analyze the overall survival (OS) benefit. Results: A total of 105,804 patients (n = 72,631 for non-Hispanic white [NHW], n = 7,632 for Hispanic white [HW], n = 19,505 for black, n = 4,393 for Asian or Pacific Islander [API], n = 1,643 for other race) were included for analysis. Median follow up was 49.2 months (interquartile range 32.7-71.3). Overall pCR rate increased from 15.1% in 2010 to 27.2% in 2017, largely driven by API women (15.7% to 31.6%) and hormone receptor (HR)-HER2+ tumors (28.6% to 53.1%; all trend p < 0.001). On logistic MVA, when compared to NHW women, HW women were more likely to have pCR for HR-HER2+ (adjusted odds ratio [aOR] 1.18, p = 0.02) and HR+HER2+ tumors (aOR 1.29, p = 0.005), while black women were more likely to have pCR for HR+HER2- tumors (aOR 1.13, p = 0.01) and less likely for HR-HER2+ (aOR 0.80, p < 0.001) and triple negative tumors (aOR 0.82, p < 0.001). API women were more likely to have pCR for HR-HER2+ tumors compared to NHW women (aOR 1.17, p = 0.04). On Cox MVA, when compared to NHW women, HW (ypT+N0: adjusted hazards ratio [aHR] 0.75, p < 0.001; ypN+: aHR 0.79, p < 0.001) and API women (ypT0/isN0: aHR 0.52, p = 0.005; ypT+N0: aHR 0.63, p < 0.001; ypN+: aHR 0.86, p = 0.03) were associated with improved OS, while black women were associated with worse OS for ypN+ only (aHR 1.18, p < 0.001). Conclusions: To our knowledge, this is the largest study using a nationwide oncology database suggesting the improving trend of pCR rate over time for all racial cohorts. In our study, when compared to NHW, HW and API women were more likely to have pCR for select HER2+ tumors, while black women were less likely to have pCR for HR-HER2+ and triple negative tumors but not for HR+HER2- tumors. HW and API women were associated with improved survival in the setting of any residual disease compared to NHW women, while black women were associated with worse survival only for residual nodal disease.

576 Background: Among patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, several prospective studies investigated various gene expression assays, such as 21-gene recurrence score (21 RS) and 70-gene signature (70 GS), to identify a subgroup of patients with pathologic complete response (pCR) from neoadjuvant chemotherapy. However, in the absence of large prospective trials to validate such findings, the National Comprehensive Cancer Network guideline does not recommend the routine adoption of such assays in the setting of neoadjuvant therapies. To address this knowledge gap, we performed an observational cohort study to compare pCR and survival outcomes based on these assays. Methods: The National Cancer Database (NCDB) was queried for female patients diagnosed between 2010 and 2017 with stage I-III breast cancer who underwent neoadjuvant chemotherapy and either 70 GS or 21 RS. Logistic multivariable analysis (MVA) was performed to identify variables associated with pCR. Cox MVA was performed to evaluate overall survival (OS). Subgroup analyses were performed among patients with favorable hormone receptor status (hormone receptor-positive, HER2-negative) and with RS ≥26 instead of RS ≥31. Results: A total of 3,009 patients met our inclusion criteria, with 2,075 (n = 1,287 for RS < 31, n = 788 for RS ≥31) and 934 (n = 175 for low risk, n = 759 for high risk) patients who underwent 21 RS and 70 GS, respectively. The median follow up was 48.0 months (interquartile range 32.2-66.7). On logistic MVA for all patients, those with a high risk from 70 GS or with RS ≥31 were more likely to have pCR. When compared to RS ≥31, a high risk from 70 GS was not associated with pCR. However, among those with favorable hormone receptor status, similar findings were noted, except that those with a high risk group from 70 GS were less likely to have pCR compared to those with RS ≥31. On Cox MVA for all patients, pCR was associated with improved OS. While RS ≥31 was associated with worse mortality, a high risk from 70 GS was not. No interaction was observed between pCR and risk groups for OS in both groups (interaction p = 0.23 for 70 GS, p = 0.66 for 21 RS). When analyses were repeated using a high risk group from 21 RS defined as RS ≥26, similar findings were noted, except that having favorable hormone receptor status and RS ≥26 was not associated with pCR when compared to the high risk from 70 GS. Conclusions: To our knowledge, this is the largest study using a nationwide oncology database suggesting that high recurrence risk groups in both assays were associated with pCR and that pCR was associated with improved survival. For those with favorable hormone receptor status, RS ≥31 may be a more selective prognostic marker. Further studies would be warranted to investigate the role of gene expression assays in the setting of neoadjuvant chemotherapy.

Objective To assess the association between financial toxicity and survival in patients with head and neck cancer (HNC). Materials and methods Using a single-institution database, we retrospectively reviewed HNC patients treated at Roswell Park Comprehensive Cancer Center treated with definitive or postoperative radiation therapy between 2013 and 2017. Kaplan-Meier method and log-rank tests were used to analyze survival outcomes. Propensity score matching on all clinically relevant baseline characteristics was performed to address selection bias. All statistical tests were two-sided and those less than 0.05 were considered statistically significant. Results Of a total of 284 HNC patients (age: median 61 years, IQR 55–67; 220 [77.5%] men), 204 patients (71.8%) received definitive radiation and 80 patients (28.2%) received adjuvant radiation. There were 41 patients (14.4%) who reported high baseline financial toxicity. Chemotherapy was used in 237 patients (83.5%). On multivariable analysis, those with high financial toxicity exhibited worse overall survival (hazards ratio [HR] 1.75, 95% confidence interval [CI] 1.05–2.94, p = 0.03) and cancer specific survival (HR 2.28, 95% CI 1.31–3.96, p = 0.003). On matched pair analysis of 66 patients, high financial toxicity remained associated with worse OS (HR 2.72, 95% CI 1.04–7.09, p = 0.04) and CSS (HR 3.75, 95% CI 1.22–11.5, p = 0.02). Conclusion HNC patient reported baseline financial toxicity was significantly correlated with both decreased overall and cancer specific survival. These significant correlations held after match pairing. Further research is warranted to investigate the impact of financial toxicity in HNC and mitigate its risk.

Neoadjuvant chemotherapy (NAC) is a significant modality in breast cancer therapy. We sought to characterize prognostic factors in patients scheduled for NAC who had a pretreatment positron-emission tomography paired with diagnostic quality contrast-enhanced computed tomography (CT) (positron-emission tomography/CT [PET/CT]). A total of 118 breast cancer patients were analyzed through chart review who underwent pretreatment PET/CT imaging and received NAC from 2008 to 2014. We collected information on molecular markers, PET/CT, pathologic complete response (pCR), survival, and disease status. Pretreatment standard uptake value (SUV) max of the primary breast tumor showed no relationship to pCR; however, there was a statistically significant relationship with relapse-free survival (RFS) using univariate cox regression (P = 0.03, odds ratio (OR) = 1.06 [1.01–1.12]) with comparable findings observed with overall survival (OS). Multivariate analysis revealed SUV max to be significantly correlated with shortened OS (P = 0.022, OR = 1.08 [1.01–1.16]), with a similar trend reported for RFS. By pathological subtype, this correlation was the strongest within hormone receptor (HR+)/human epidermal growth factor receptor 2 (HER2−) tumors. In addition, Kaplan–Meier estimates demonstrated a significant difference between the RFS of triple-negative tumors and HER2 positive tumors (P = 0.001). Interestingly, within this cohort, multivariate Cox regression analysis showed HER2 positivity to be associated with favorable outcome (P = 0.04, HR = 0.22 [0.05–0.94]). These findings demonstrate a significant association between SUV max of HR+/HER2−− tumors and relapse-free and OS. Furthermore, highlighted here is the favorable survival in the once classically aggressive HER2+ breast cancer subgroup.

Food allergies encompass a range of disorders ranging from being an inconvenience to even causing fatalities, mainly due to anaphylaxis. A large number of individuals are affected and this presents great health and economic implications. However as yet, apart from dietary avoidance, effective treatment strategies are practically non-existent. The immune environment related to allergen-tolerance is highly complex and the role of regulatory T-cells in allergenspecific tolerance, their interaction with other cells in inflamed tissues, and their role in antibody regulation have been demonstrated in several studies. Regulatory T-cells are able to control acquired immunity and achieve oral tolerance to food allergens. Immunotherapy for food allergies focuses on desensitisation by increasing the allergen reactivity threshold. So far, the only long-term curative treatment used effectively is allergen-specific immunotherapy which involves the administration of increasing doses of the causative allergen, such that a state of allergen-specific immune tolerance is induced over the course of the treatment. This review covers various forms of allergen-specific immunotherapy, focusing on the role of regulatory T-cells in such therapies, and includes a number of small studies providing ideas for future work in the area., peer-reviewed

The autoimmune disorder rheumatoid arthritis (RA) causes chronic inflammation and destruction of joints. T cells are a predominant component of the synovial environment in RA, however the functional role of these cells is not yet fully understood. This is in part due to the fact that the balance and importance of the relation of Tregs with T-effector cells in RA is still under investigation. The current treatment regimen for this debilitating disease focuses on controlling symptoms and preventing further joint damage through the use of therapies which affect different areas of the immune system at the synovium. One of the main therapies involves Tumor Necrosis Factor alpha (TNF-α) inhibitors. In the RA immune-environment, TNF-α has been shown to have an influential and extensive but as yet poorly understood effect on Treg function in vivo, and undoubtably an important role in the treatment of RA. Interestingly, the high levels of TNF-α found in RA patients appear to interfere with the mechanisms controlling the suppressive function of Tregs. Relevance for patients: This review focuses on the conflicting literature available regarding the role played by Tregs in RA and the impact of TNF-α and anti-TNF-α therapies on Tregs in this scenario. Individuals suffering from RA can benefit from better insight of the treatment mechanisms of the immunologic processes which occur throughout this disease, as current treatments for RA focus on several different areas of the immune system at the synovial compartment., peer-reviewed

Summary A 44-year-old female presented with a 3-month history of headache, dizziness, nausea, and vomiting. Her past medical history was significant for long-standing intravenous drug abuse. Shortly after admission, the patient became hypertensive and febrile, with fever as high as 38.8°C. The lumbar puncture profile supported an infectious process; however multiple cultures of blood and cerebrospinal fluid (CSF) did not initially show growth of organisms. Finally after 9 days of incubation, a CSF culture showed evidence of a few colonies of Candida albicans . To confirm the diagnosis, preserved CSF from that sample was tested for (1→3)-β-d-glucan, showing levels >500pg/ml. This report illustrates a rare complication of intravenous drug use in an immunocompetent patient and demonstrates the utility of (1→3)-β-d-glucan testing in possible Candida meningitis.

e12113 Background: Neoadjuvant chemotherapy (NAC) is an important modality in breast cancer treatment. We sought to identify pre-treatment prognostic factors in patients who had positron emission tomography paired with diagnostic quality contrast-enhanced CT (PET/CT) prior to neoadjuvant chemotherapy with respect to pathologic complete response (pCR) , survival and relapse-free survival (RFS). Methods: We retrospectively analyzed 118 breast cancer patients who had pre-treatment PET/CT imaging and received NAC from 2008-2014. We collected data on molecular markers, PET/CT, pCR, survival, and disease status. Results: The median follow up was 44 months(range 7.3-101.5),median age was 51 years; 47% were stage II, 53% stage III. 52% of patients had hormone receptor (HR) positive/HER2 negative disease, 31% of tumors were HER2 positive, and 17% of tumors were triple-negative. 92.5% with HER2 positive tumors received NAC containing at least one HER2 targeted agent. Pre-treatment standard uptake value (SUV) max of the primary breast tumor showed no statistically significant relationship to survival, RFS, or pCR. PET avid (>2 SUV) extra-axillary nodes such as internal mammary and supraclavicular was associated with a non-statistically significant trend towards reduced RFS (p=0.06, HR=0.13-1.06). pCR overall was 37.5% for HER2 positive tumors, 15% in triple-negative tumors, and 8% in HR positive/HER2 negative tumors. Log-rank analysis with post-hoc pairwise comparisons showed a significant difference between the RFS of triple-negative tumors and HER2 positive tumors (p=0.001), while comparison between HR positive/HER2 negative and HER2 positive was not statistically significant (p=0.11). Multivariate cox regression analysis, which included grade and stage of tumors, showed HER2 positivity to be associated with a favorable outcome (p=0.04, HR=0.22 (0.05-0.94)). Conclusions: Within this cohort, pre-treatment SUV max of the primary tumor showed no prognostic value with regard pCR or RFS. PET avid extra-axillary metastasis trended towards reduced RFS. Patients with HER2 positive tumors had the highest pCR and RFS comparable to classically favorable subgroups such as HR positive/HER 2 negative.