Systemic Immune-Inflammatory Index Association with Survival in Patients Undergoing Trimodality Therapy for Lung Cancer.

PURPOSE: The systemic immune-inflammation index (SII) is correlated with patient survival in various solid malignancies including non-small-cell lung cancer (NSCLC). However, limited information is available on the prognostic implication of the SII in patients undergoing trimodality therapy for stage III NSCLC. METHODS: At our institution, 81 patients underwent curative intent trimodality therapy (neoadjuvant chemoradiotherapy followed by surgical resection) for stage III NSCLC from 2004 to 2019. The SII was calculated at the time of diagnosis as platelet count × neutrophil count/lymphocyte count. χ2 analysis was used to compare categorical variables. A Kaplan-Meier analysis was performed to estimate disease-free survival (DFS), overall survival (OS), and freedom from recurrence (FFR) rates, with Cox regression used to determine absolute hazards. RESULTS: Patients underwent neoadjuvant radiation therapy to a median dose of 4,500 cGy concurrent with a median of 3 cycles of chemotherapy (most commonly carboplatin and paclitaxel) followed by surgical resection (86.4% lobectomy and 13.6% pneumonectomy) with mediastinal lymph node dissection. At a median follow-up of 68.4 months, a low SII (<1,260) at diagnosis was independently associated with an improved OS (hazard ratio [HR]: 0.448, p = 0.004), DFS (HR: 0.366, p < 0.001), and FFR (HR: 0.325, p = 0.002). CONCLUSIONS: We identified that a low SII was associated with improved OS, DFS, and FFR in patients undergoing trimodality therapy for stage III NSCLC. The interplay of the immune system and lung cancer outcomes remains an active area of investigation for which further study is warranted.

Impact of statin use on overall and time to biochemical failure following radical prostatectomy or radiation therapy.

OBJECTIVES: To assess the impact of statin use on overall and time to biochemical failure following primary treatment of localized prostate cancer (PCa). SUBJECTS/PATIENTS AND METHODS: 1581 patients undergoing radical prostatectomy (RP) or radiation therapy (RT) for primary treatment of PCa between July 2007 and January 2020 were evaluated for statin use, demographic/oncologic characteristics, and biochemical outcomes. Rate of biochemical failure (BF) was assessed overall and at 1, 3, and 5 years; time to BF was estimated with Kaplan-Meier. Logistic and linear regression were used to control for treatment modality and disease characteristics. RESULTS: The average age was 63.0 ± 7.5 years and median pre-treatment PSA was 6.55 (IQR 4.94). 1473 (93.2%) and 108 (6.8%) underwent RP and RT, respectively. RP patients were younger, had lower pre-PSA, lower BMI, and lower risk disease. At 3.4 ± 2.7 years follow-up, 323 (20.4%) experienced BF. When stratified by statin use, BF overall and within 1, 3, and 5 years were not different. Time to BF, was lower in patients using statins (1.8 ± 1.9 years vs. 2.4 ± 2.6 years; p = 0.016). These results persisted in multivariate analysis, wherein statin use was not associated with BF but was associated with a shorter time to BF. CONCLUSION: Overall, statin use was not associated with a reduced risk of BF in RP or RT patients. However, for patients with BF, statin use was associated with a decreased time to BF. Future investigations are warranted to further elucidate the impact of statin use on PCa recurrence.

Efficacy of sequential radiation and chemotherapy in treating glioblastoma with poor performance status.

INTRODUCTION: While the current standard of care after maximal safe resection for glioblastoma (GBM) is concomitant radiation and chemotherapy, the ideal therapy for patients with poor performance status remains in question due to concerns about treatment tolerance. We sought to evaluate an alternative regimen, sequential radiation and chemotherapy, to assess its efficacy as a treatment option for poorly performing patients. METHODS: We performed a retrospective analysis using the 2015 National Cancer Database in which the survival of patients with a KPS ≤ 70 who received sequential radiation and chemotherapy were compared to those who received radiation therapy alone. Survival outcomes were compared using Kaplan-Meier curves with log rank testing and Cox proportional hazard regression. RESULTS: There were 84 patients analyzed in this study, all of whom had a KPS between 10 and 70. Of those analyzed, 73.8% received radiation therapy alone, and 26.2% received sequential radiation and chemotherapy. There was no difference in survival between the two treatment groups (p = 0.84). Patient age of 70 years or older (n = 31) was associated with decreased survival (HR 1.06 per year, p < 0.0001), regardless of KPS and a KPS of < 70 correlated with a near-significant trend toward worse survival (HR 1.63, p = 0.06). CONCLUSIONS: Treatment with sequential radiation and chemotherapy in poorly performing patients is not associated with an advantage in survival outcome when compared to radiation alone in GBM patients with poor performance status.

Biological determinants of radioresistance and their remediation in pancreatic cancer.

Despite recent advances in radiotherapy, a majority of patients diagnosed with pancreatic cancer (PC) do not achieve objective responses due to the existence of intrinsic and acquired radioresistance. Identification of molecular mechanisms that compromise the efficacy of radiation therapy and targeting these pathways is paramount for improving radiation response in PC patients. In this review, we have summarized molecular mechanisms associated with the radio-resistant phenotype of PC. Briefly, we discuss the reversible and irreversible biological consequences of radiotherapy, such as DNA damage and DNA repair, mechanisms of cancer cell survival and radiation-induced apoptosis following radiotherapy. We further describe various small molecule inhibitors and molecular targeting agents currently being tested in preclinical and clinical studies as potential radiosensitizers for PC. Notably, we draw attention towards the confounding effects of cancer stem cells, immune system, and the tumor microenvironment in the context of PC radioresistance and radiosensitization. Finally, we discuss the need for examining selective radioprotectors in light of the emerging evidence on radiation toxicity to non-target tissue associated with PC radiotherapy.

Lymphocyte-sparing effect of stereotactic body radiation therapy compared to conventional fractionated radiation therapy in patients with locally advanced pancreatic cancer.

BACKGROUND: Conventionally fractionated (CF) radiation therapy (RT) has been associated with lymphopenia, leading to compromised overall survival (OS) in cancer patients. It currently remains unknown if stereotactic body (SB) RT induces lymphopenia to the same degree. The aim of this study is to determine if SBRT with either chemotherapy (CMT) (Fluorouracil (5FU) or capecitabine) or Nelfinavir (NFV) to pancreatic adenocarcinoma induces lymphopenia to the same degree as CFRT with 5FU or capecitabine and how any associated difference affects patient survival outcomes. METHODS: Medical records of pancreatic adenocarcinoma patients treated with induction CMT followed by RT with concurrent CMT or NFV were reviewed. Patients with total lymphocyte counts (TLCs) available both prior to and following initiation of RT were included. Three groups were identified: CFRT/CMT, SBRT/CMT, and SBRT/NFV. Median delivered RT doses for CFRT and SBRT were 50.4 Gy in 1.8 Gy fractions and 35 Gy in 7 Gy fractions, respectively. TLCs from day 0 (the first day of RT) to 40 were recorded and analyzed using the Kruskal-Wallis test with p-values adjusted with Bonferroni's method. Linear regressions were utilized to estimate the slope of TLCs as it changes with time and survival analysis was performed via Kaplan-Meier plots. RESULTS: One hundred patients were identified (28 CFRT/CMT, 27 SBRT/CMT, 45 SBRT/NFV). Median pre-RT TLCs were not different among groups. Median lowest TLCs were significantly lower (p <  0.0001) and median TLCs reduction over time were significantly greater (p <  0.0001) in the CFRT group than SBRT groups. There was no difference in lowest TLCs or TLCs reduction over time between SBRT groups. Across all groups, the median time to lowest TLCs was similar. Survival analysis revealed no significant difference in median OS between SBRT and CFRT groups. However, in patients with surgery, Median OS for patients with SBRT/CMT was significantly higher than in those with SBRT/NFV (p = 0.03). CONCLUSIONS: Compared to CFRT, SBRT is associated with less lymphopenia. Further study of the effect of radiation technique on immune status is warranted.

Stereotactic Body Radiation Therapy Versus Nonradiotherapeutic Ablative Procedures (Laser/Cryoablation and Electrocautery) for Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: Despite the fact that stereotactic body radiation therapy (SBRT) is the only recommended first-line therapy for inoperable early-stage non-small cell lung cancer (NSCLC), several thermal ablative procedures (TAPs; defined herein as laser/cryoablation and electrocautery) are available. Studies showing outcomes of these procedures and how they compare with SBRT are scarce. We sought to evaluate the comparative efficacy of SBRT versus TAPs using the National Cancer Database (NCDB). METHODS: The NCDB was queried for patients with early-stage NSCLC who did not undergo surgical resection. Treatment-specific inclusion criteria were applied to select for patients receiving either TAPs or SBRT. Univariate logistic regression and Cox proportional hazards modeling were performed, and Kaplan-Meier curves were generated. Serial propensity matches were performed using a modified greedy 8→n matching 1:1 algorithm. RESULTS: A total of 27,734 patients were analyzed; 26,725 underwent SBRT and 1,009 underwent TAPs. Patients who received SBRT were older and more likely to have clinical stage IB (vs IA) disease. Despite this, SBRT was associated with longer median overall survival (mOS; 37.7 vs 33.5 months; P=.001) and 1-, 2-, and 5-year OS rates compared with the TAPs cohort (86.7% vs 83.1%, 67.5% vs 62.7%, and 30.6% vs 26.9%, respectively; P=.001). Upon propensity matching, improved OS with SBRT remained, with a mOS of 40.4 versus 33.4 months and 1-, 2-, and 5-year OS rates of 89.0% versus 82.9%, 69.7% versus 62.7%, and 34.4% versus 26.4%, respectively (P=.003). CONCLUSIONS: Despite being associated with more higher-risk factors, SBRT was associated with higher OS compared with TAPs for treatment of nonoperative patients diagnosed with early-stage NSCLC. However, causation cannot be implied owing to the inherent limitations of large heterogeneous datasets such as the NCDB.

Exogenous APN protects normal tissues from radiation-induced oxidative damage and fibrosis in mice and prostate cancer patients with higher levels of APN have less radiation-induced toxicities.

Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage invitro and invivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice. Importantly, APN also conferred no protection from radiation to prostate cancer cells. Adipose tissue is the primary source of circulating endogenous adiponectin. However, this study shows that adipose tissue is sensitive to radiation exposure exhibiting morphological changes and persistent oxidative damage. In addition, radiation results in a significant and chronic reduction in blood APN levels from adipose tissue in mice and human prostate cancer patients exposed to pelvic irradiation. APN levels negatively correlated with bowel toxicity and overall toxicities associated with radiotherapy in prostate cancer patients. Thus, protecting, or modulating APN signaling may improve outcomes for prostate cancer patients undergoing radiotherapy.

Radiation therapy for pineal parenchymal tumor of intermediate differentiation: A case series and literature review.

Pineal parenchymal tumor of intermediate differentiation (PPTID) is a rare, primary tumor of the pineal gland. Due to its rarity, there is no consensus on optimal therapeutic strategies or standard characterization of the tumor's behavior. Here, we report 2 new cases of PPTID and an extensive review of the literature involving the use and extent of radiation therapy. Patient 1 is a 54-year-old male who presented with PPTID and drop metastases in the spinal cord, received cranial spinal irradiation (CSI), and experienced recurrence 3.5 years after treatment. Stereotactic body radiation therapy (SBRT) helped the patient into remission for 9 months. Patient 2 is a 32-year-old male with a local PPTID at presentation who went on to receive surgical resection followed by focused adjuvant radiation therapy to the pineal tumor bed. He then presented 6 years after treatment with extensive disseminated recurrence and died due to leptomeningeal disease (LMD) about 4 years after recurrence. The available literature on PPTID is limited and reported cases of LMD with ongoing follow-up in PPTID are scarce. Our report adds to the current known PPTID cases, contributing to the information available regarding prognosis and treatment response. Although an optimal therapeutic strategy for PPTID still cannot be determined, data from the literature suggest that utilizing radiation therapy in patients with low-risk disease and gross total resections as well as the use of upfront CSI have the potential to improve patient progression and survival outcomes.

The Association of Immunotherapy With the Overall Survival of Inoperable Stage III Non-small Cell Lung Cancer Patients Who Do Not Receive Chemoradiation.

Immunotherapy has been approved for stage III non-small cell lung cancer (NSCLC) as consolidation therapy after chemoradiation in patients whose disease does not progress after chemoradiation. However, many patients do not receive chemoradiation due to either the drugs' side effects or poor performance status. This study's objective is to investigate the association of immunotherapy combined with chemotherapy or Radiotherapy (RT) with the overall survival (OS) of stage III NSCLC patients who do not receive chemoradiation. Patients with stage III NSCLC who received either chemotherapy or RT with or without immunotherapy were identified from NCDB. The Cox proportional hazard regression analysis was implied to assess the effect of immunotherapy on survival after adjusting the model for age at diagnosis, race, sex, education, treatment facility type, insurance status, comorbidity score, histology year of diagnosis, and treatment types, such as chemotherapy and radiation therapy. The final analysis included 32,328 patients, among whom 3,205 (9.9%) received immunotherapy. In the multivariable analysis adjusted for all the factors previously mentioned, immunotherapy was associated with significantly improved OS (HR: 0.76, CI: 0.71-0.81) compared with no immunotherapy. Treatment with chemotherapy plus immunotherapy was significantly associated with improved OS (HR: 0.83, CI: 0.77-0.90) compared with chemotherapy without immunotherapy. Further, RT plus immunotherapy was associated with significantly improved OS (HR: 0.62, CI: 0.54-0.70) compared with RT alone. In this comprehensive analysis, the addition of immunotherapy to chemotherapy or radiotherapy was associated with improved OS compared with chemotherapy or radiation therapy without immunotherapy in stage III NSCLC patients.

The Use of MRI-Derived Radiomic Models in Prostate Cancer Risk Stratification: A Critical Review of Contemporary Literature.

The development of precise medical imaging has facilitated the establishment of radiomics, a computer-based method of quantitatively analyzing subvisual imaging characteristics. The present review summarizes the current literature on the use of diagnostic magnetic resonance imaging (MRI)-derived radiomics in prostate cancer (PCa) risk stratification. A stepwise literature search of publications from 2017 to 2022 was performed. Of 218 articles on MRI-derived prostate radiomics, 33 (15.1%) generated models for PCa risk stratification. Prediction of Gleason score (GS), adverse pathology, postsurgical recurrence, and postradiation failure were the primary endpoints in 15 (45.5%), 11 (33.3%), 4 (12.1%), and 3 (9.1%) studies. In predicting GS and adverse pathology, radiomic models differentiated well, with receiver operator characteristic area under the curve (ROC-AUC) values of 0.50-0.92 and 0.60-0.92, respectively. For studies predicting post-treatment recurrence or failure, ROC-AUC for radiomic models ranged from 0.73 to 0.99 in postsurgical and radiation cohorts. Finally, of the 33 studies, 7 (21.2%) included external validation. Overall, most investigations showed good to excellent prediction of GS and adverse pathology with MRI-derived radiomic features. Direct prediction of treatment outcomes, however, is an ongoing investigation. As these studies mature and reach potential for clinical integration, concerted effort to validate these radiomic models must be undertaken.

3DGAUnet: 3D Generative Adversarial Networks with a 3D U-Net Based Generator to Achieve the Accurate and Effective Synthesis of Clinical Tumor Image Data for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents a critical global health challenge, and early detection is crucial for improving the 5-year survival rate. Recent medical imaging and computational algorithm advances offer potential solutions for early diagnosis. Deep learning, particularly in the form of convolutional neural networks (CNNs), has demonstrated success in medical image analysis tasks, including classification and segmentation. However, the limited availability of clinical data for training purposes continues to represent a significant obstacle. Data augmentation, generative adversarial networks (GANs), and cross-validation are potential techniques to address this limitation and improve model performance, but effective solutions are still rare for 3D PDAC, where the contrast is especially poor, owing to the high heterogeneity in both tumor and background tissues. In this study, we developed a new GAN-based model, named 3DGAUnet, for generating realistic 3D CT images of PDAC tumors and pancreatic tissue, which can generate the inter-slice connection data that the existing 2D CT image synthesis models lack. The transition to 3D models allowed the preservation of contextual information from adjacent slices, improving efficiency and accuracy, especially for the poor-contrast challenging case of PDAC. PDAC's challenging characteristics, such as an iso-attenuating or hypodense appearance and lack of well-defined margins, make tumor shape and texture learning challenging. To overcome these challenges and improve the performance of 3D GAN models, our innovation was to develop a 3D U-Net architecture for the generator, to improve shape and texture learning for PDAC tumors and pancreatic tissue. Thorough examination and validation across many datasets were conducted on the developed 3D GAN model, to ascertain the efficacy and applicability of the model in clinical contexts. Our approach offers a promising path for tackling the urgent requirement for creative and synergistic methods to combat PDAC. The development of this GAN-based model has the potential to alleviate data scarcity issues, elevate the quality of synthesized data, and thereby facilitate the progression of deep learning models, to enhance the accuracy and early detection of PDAC tumors, which could profoundly impact patient outcomes. Furthermore, the model has the potential to be adapted to other types of solid tumors, hence making significant contributions to the field of medical imaging in terms of image processing models.

Multi-Institutional Development and Validation of a Radiomic Model to Predict Prostate Cancer Recurrence Following Radical Prostatectomy.

The use of multiparametric magnetic resonance imaging (mpMRI)-derived radiomics has the potential to offer noninvasive, imaging-based biomarkers for the identification of subvisual characteristics indicative of a poor oncologic outcome. The present study, therefore, seeks to develop, validate, and assess the performance of an MRI-derived radiomic model for the prediction of prostate cancer (PC) recurrence following radical prostatectomy (RP) with curative intent. mpMRI imaging was obtained from 251 patients who had undergone an RP for the treatment of localized prostate cancer across two institutions and three surgeons. All patients had a minimum of 2 years follow-up via prostate-specific antigen serum testing. Each prostate mpMRI was individually reviewed, and the prostate was delineated as a single slice (ROI) on axial T2 high-resolution image sets. A total of 924 radiomic features were extracted and tested for stability via intraclass correlation coefficient (ICC) following image normalization via histogram matching. Fourteen important and nonredundant features were found to be predictors of PC recurrence at a mean ± SD of 3.2 ± 2.2 years post-RP. Five-fold, ten-run cross-validation of the model containing these fourteen features yielded an area under the curve (AUC) of 0.89 ± 0.04 in the training set (n = 225). In comparison, the University of California San Fransisco Cancer of the Prostate Risk Assessment score (UCSF-CAPRA) and Memorial Sloan Kettering Cancer Center (MSKCC) Pre-Radical prostatectomy nomograms yielded AUC of 0.66 ± 0.05 and 0.67 ± 0.05, respectively (p < 0.01). When the radiomic model was applied to the test set (n = 26), AUC was 0.78; sensitivity, specificity, positive predictive value, and negative predictive value were 60%, 86%, 52%, and 89%, respectively. Accuracy in predicting PC recurrence was 81%.

Comparison of sequential versus concurrent chemoradiation regimens in non-metastatic muscle-invasive bladder cancer.

PURPOSE: The treatment approach for non-metastatic bladder cancer is guided by an invasion of the muscular layer of the bladder wall. Radical cystectomy is the recommended treatment for muscle-invasive disease. However, it has considerable morbidity and mortality and is not suited for many patients. Trimodality therapy consisting of chemoradiation after transurethral resection of bladder tumor offers a definitive approach with bladder-sparing potential. However, there is a lack of research defining the optimal combination of chemotherapy and radiation in this setting. MATERIALS AND METHODS: We extracted patient data from the National Cancer Database to compare survival outcomes and demographic factors in 2,227 non-metastatic bladder cancer patients who were treated with chemotherapy sequential to or concurrently with radiation. Sequential treatment was defined as chemotherapy beginning >14 days before radiation, and concurrent was defined as beginning within 14 days of the first radiation. RESULTS: The sequential treatment group patients were younger (mean age, 74 vs. 78 years; p < 0.001) with more advanced disease. We found no difference in overall survival between patients who received chemotherapy sequential to radiation and those who received concurrent chemoradiation only (p = 0.533). CONCLUSION: Our data are concordant with a previous prospective study, and support that chemotherapy prior to radiation does not decrease survival outcomes relative to patients receiving only concurrent chemoradiation. Given that the sequential group had an overall higher stage but no difference in survival, downstaging chemotherapy prior to radiation may be helpful in these patients. Further studies including a larger, multi-institutional clinical trial are indicated to support clinical decision-making.

Current status of molecular markers for early detection of sporadic pancreatic cancer.

Pancreatic cancer (PC) is a highly lethal malignancy with near 100% mortality. This is in part due to the fact that most patients present with metastatic or locally advanced disease at the time of diagnosis. Significantly, in nearly 95% of PC patients there is neither an associated family history of PC nor of diseases known to be associated with an increased risk of PC. These groups of patients who comprise the bulk of PC cases are termed as "sporadic PC" in contrast to the familial PC cases that comprise only about 5% of all PCs. Given the insidious onset of the malignancy and its extreme resistance to chemo and radiotherapy, an abundance of research in recent years has focused on identifying biomarkers for the early detection of PC, specifically aiming at the sporadic PC cohort. However, while several studies have established that asymptomatic individuals with a positive family history of PC and those with certain heritable syndromes are candidates for PC screening, the role of screening in identifying sporadic PC is still an unsettled question. The present review attempts to assess this critical question by investigating the recent advances made in molecular markers with potential use in the early diagnosis of sporadic PC - the largest cohort of PC cases worldwide. It also outlines a novel yet simple risk factor based stratification system that could be potentially employed by clinicians to identify those individuals who are at an elevated risk for the development of sporadic PC and therefore candidates for screening.

Pathologic Characteristics Associated With Local Recurrence of Atypical Meningiomas Following Surgical Resection.

BACKGROUND: Optimal management of grade II meningiomas following resection remains controversial, owing mostly to the heterogeneity of post-operative (post-op) recurrence patterns across studies. Improved risk stratification of these patients would ensure that only those most at risk of recurrence would undergo appropriate post-op radiation therapy (RT). METHODS: Medical records from patients who underwent resection for grade II meningiomas were retrospectively reviewed. Demographic, disease characteristics, treatment, and clinical course data were retrospectively collected. Logistic regression, Cox proportional hazards modeling, and Kaplan-Meier curves with log rank testing were conducted to describe any potential relationships with time of recurrence. RESULTS: Of the 49 patients identified, 18 (36.7%) suffered a local recurrence following resection with a median follow-up of 3.1 years (range: 0.23 - 17.1 years). Past recurrence of the meningioma (P = 0.002) and extent of resection (P = 0.02) were significantly associated with local recurrence. On multivariable analysis, only prior meningioma recurrence was associated with time to local failure (P = 0.021). No histopathologic factors were found to be associated with the initial local failure. Of those who suffered a local recurrence, the presence of bone invasion (hazard ratio: 0.069, P = 0.008) and lack of salvage RT (P = 0.02) were associated with subsequent local failure. CONCLUSIONS: Currently considered histopathologic factors appear not to be helpful in guiding initial treatment course. History of prior local failure and bone invasion appear to be associated with multiple recurrences. Optimal surgical resection is critical to improving outcomes, and salvage RT may reduce subsequent local failure.

Development of bullous pemphigoid following radiation therapy combined with nivolumab for renal cell carcinoma: A case report of abscopal toxicities.

RATIONALE: Concern for immune-related adverse events from immunotherapy and radiation therapy are well-documented; however, side effects are mostly mild to moderate. However, high-grade, potentially life-threatening adverse events are increasing. While case reports regarding immunotherapy-related bullous pemphigoid (BP) have been rising, only 1 has described BP following concomitant use of both nivolumab and radiation therapy (RT). For that patient, nivolumab was used for 10 weeks prior to RT and development of PB followed 7 weeks later. This case presents a patient who tolerated nivolumab well for 38 months prior to developing BP less than 2 weeks after completing RT. PATIENT CONCERNS: We present the case of DH, a 67-year-old gentleman on nivolumab for metastatic renal cell carcinoma to the lung since May of 2017. Following progressing lung nodules, the patient had his nivolumab paused and completed a course of short-beam radiation therapy. After restarting nivolumab post-radiation, the patient presented with itchy rash and blisters on his arm, legs, and trunk. DIAGNOSIS: DH consulted dermatology following development of rash and was diagnosed with bullous dermatosis, likely bullous pemphigoid. Bullous pemphigoid following concomitant nivolumab (OPDIVO), despite prior tolerance and no history of autoimmune disease, was confirmed by biopsy a month later. INTERVENTIONS: Initial treatment was betamethasone 0.05% cream mixed 1:1 with powder to form paste applied twice daily. Given progressive symptoms and confirmatory biopsy of BP, nivolumab was held and 100 mg doxycycline and 80 mg prednisone daily was prescribed for a week, reduced to 60 mg during the second week. OUTCOMES: A week following discontinuation of nivolumab and beginning of doxycycline and prednisone, the blistering and rash was almost entirely resolved. Four months later, nivolumab was restarted and the patient continued low-dose tapering of prednisone until December. Since completing prednisone, the patient has shown no recurrence of bullous pemphigoid and has not developed any other immune-related adverse events to nivolumab upon rechallenge. Follow-up through October 2021 demonstrates the patient's sites of disease, both in- and out-field, have remained responsive to treatment. LESSONS: Treating physicians should be aware of off-target effects of radiotherapy for oligoprogressive disease, which may include abscopal toxicities and the development of new immune-related adverse effects.

The impact of stereotactic body radiation therapy on the overall survival of patients diagnosed with early-stage non-small cell lung cancer.

BACKGROUND AND PURPOSE: Stereotactic Body Radiotherapy (SBRT) has emerged as a standard treatment for inoperable early-stage non-small cell lung cancer (NSCLC) with remarkable local control. However, it is not clear if this local control translates to overall survival (OS). The objective of this study is to investigate the impact of SBRT on the OS of early-stage NSCLC patients and examine if the extent of this impact changes with the era of diagnosis, T stage, age, and comorbidity status. MATERIALS AND METHODS: Using the National Cancer Database, we compared the OS of cT1-3 cN0 cM0 NSCLC patients with SBRT or observation. Multivariable analyses were adjusted for age, race, sex, income, education, place of living, hospital type, insurance status, comorbidity score, histology types, and diagnosis year. RESULTS: Among 50,819 patients, 27,027 (53.18%) received SBRT and 23,792 (46.82%) were observed. Multivariable Cox Proportional-Hazards analysis demonstrated SBRT was associated with an improved OS compared to observation (HR:0.56, p < 0.001). Subset multivariable Cox Proportional-Hazards analyses stratified by T stage, year of diagnosis, age, or Charlson Score revealed that HRs of SBRT vs. observation decrease from cT1 to cT3 (0.73-0.68), from 2004 to 2015 (0.65-0.51), from <50 to ≥80 years old (1.04-0.58) and from a Charlson Score 0 to 2 (0.69-0.58). CONCLUSION: SBRT was associated with improved OS compared to no treatment in early-stage NSCLC. The magnitude of the impact of SBRT on OS increases in patients with advanced age, higher T stages, higher comorbidity scores and more recent treatment eras.

The timing and design of stereotactic radiotherapy approaches as a part of neoadjuvant therapy in pancreatic cancer: Is it time for change?

Stereotactic Radiotherapy (SRT) over 5-15 days can be interdigitated without delaying chemotherapy. Bridging chemotherapy may allow for extended intervals to surgery, potentially improving sterilization of surgical margins and overall survival. SRT for pancreatic adenocarcinoma should not be limited to the tumor, and should consider hypofractionated approaches to regional nodes.

Diffuse lesions secondary to sarcoidosis mimicking widespread metastatic breast cancer: A case report.

This case of sarcoidosis mimicking metastatic breast cancer serves as a reminder of the need to consider differential diagnoses even when the clinical scenario and imaging findings are highly suggestive of metastases.

p53/FBXL20 axis negatively regulates the protein stability of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase.

We have previously reported an important role of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase, in the support of critical oncogenic pathways required for oncogenesis and the malignant phenotype of pancreatic cancer. The studies in this report reveal a novel mechanism by which the p53 tumor suppressor inhibits the protein-stability of PR55α via FBXL20, a p53-target gene that serves as a substrate recognition component of the SCF (Skp1_Cullin1_F-box) E3 ubiquitin ligase complex that promotes proteasomal degradation of its targeted proteins. Our studies show that inactivation of p53 by siRNA-knockdown, gene-deletion, HPV-E6-mediated degradation, or expression of the loss-of-function mutant p53R175H results in increased PR55α protein stability, which is accompanied by reduced protein expression of FBXL20 and decreased ubiquitination of PR55α. Subsequent studies demonstrate that knockdown of FBXL20 by siRNA mimics p53 deficiency, reducing PR55α ubiquitination and increasing PR55α protein stability. Functional tests indicate that ectopic p53R175H or PR55α expression results in an increase of c-Myc protein stability with concomitant dephosphorylation of c-Myc-T58, which is a PR55α substrate, whose phosphorylation otherwise promotes c-Myc degradation. A significant increase in anchorage-independent proliferation is also observed in normal human pancreatic cells expressing p53R175H or, to a greater extent, overexpressing PR55α. Consistent with the common loss of p53 function in pancreatic cancer, FBXL20 mRNA expression is significantly lower in pancreatic cancer tissues compared to pancreatic normal tissues and low FBXL20 levels correlate with poor patient survival. Collectively, these studies delineate a novel mechanism by which the p53/FBXL20 axis negatively regulates PR55α protein stability.