Invasive squamous cell carcinoma of the breast associated with breast augmentation implant capsule.

Primary squamous cell carcinoma (SCC) of the breast is rare, representing less than 0.1% of all breast cancers. To date, there have been 20 reported cases of SCC associated with breast augmentation, usually in patients with long-standing implants. A patient is reported here with primary squamous carcinoma of the breast associated with textured saline implants. Due to the paucity of cases, there is limited information on the incidence and management of implant-associated SCC of the breast.

Axillary lymph node recurrence following wire-directed sentinel lymph node dissection for breast cancer patients with biopsy-proven axillary metastases prior to neoadjuvant chemotherapy at a safety net medical center.

BACKGROUND: Although sentinel lymph node dissection (SLND) after neoadjuvant chemotherapy (NAC) is feasible, axillary management for patients with pretreatment biopsy-proven axillary metastases and who are clinically node-negative after NAC (ycN0) remains unclear. This retrospective study was performed to determine the rate of axillary lymph node recurrence for such patients who had wire-directed (WD) SLND. METHODS: Patients treated with NAC from 2015 to 2020 had axillary nodes evaluated by pretreatment ultrasound. Core biopsies were done on abnormal nodes, and microclips were placed in nodes during biopsy. For patients with biopsy-proven node metastases who received NAC and were ycN0 by clinical exam, WD SLND was done. Patients with negative nodes on frozen section had WD SLND alone; those with positive nodes had WD SLND plus axillary lymph node dissection (ALND). RESULTS: Of 179 patients receiving NAC, 62 were biopsy-proven node-positive pre-NAC and ycN0 post-NAC. Thirty-five (56%) patients were node-negative on frozen section and had WD SLND alone. Twenty-seven (43%) patients had WD SLND + ALND. Forty-seven patients had postoperative regional node irradiation. With median follow-up of 40 months, there were recurrences in 4 (11%) of 35 patients having WD SLND and 5 (19%) of 27 having WD SLND + ALND, but there was only one axillary lymph node recurrence, identified by CT scan. CONCLUSIONS: Axillary node recurrence was very uncommon after WD SLND for patients who had pretreatment biopsy-proven node metastases and were ypN0 after NAC. These patients would be unlikely to derive clinical benefit from the addition of completion ALND to SLND.

Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity.

INTRODUCTION: There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases. METHODS: We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan-Meier method. OS was analyzed with Cox regression. RESULTS: Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab. CONCLUSIONS: Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.

Is there an impact of heart exposure on the incidence of radiation pneumonitis? Analysis of data from a large clinical cohort.

BACKGROUND: The goal of the present study was to determine, in a large clinical cohort, whether incidental radiation exposure to the heart during definitive radiotherapy of inoperable non-small cell lung cancer (NSCLC) detectably increased the risk of radiation pneumonitis (RP) beyond that resulting from radiation exposure to lung. MATERIAL AND METHODS: Data were analyzed from all patients who received definitive three-dimensional (3D) concurrent radiotherapy or intensity-modulated radiotherapy for the treatment of NSCLC over a 10-year period at our institution, except those who had previous lung cancer or for whom radiation treatment plans were unavailable for calculation of heart and lung dose-volume histograms (DVHs). Parameters computed from heart and lung DVHs included mean lung dose (MLD), effective lung dose computed using volume parameter n = 0.5 (Deff), mean heart dose (MHD), percentage of heart receiving > 65 Gy (V65), and minimum dose to the hottest 10% of heart (D10). Univariate and multivariate normal-tissue complication probability (NTCP) models were used to analyze incidence of Grade ≥ 2 or Grade ≥ 3 RP as a function of these and other parameters. RESULTS: The study cohort included 629 patients, with crude rates of Grade ≥ 2 RP and Grade ≥ 3 RP of N = 263 (42%) and N = 124 (20%), respectively. Univariate NTCP models based on dosimetric lung parameters (MLD and Deff) fit the data better than models based on univariate heart parameters (heart D10, heart V65 or MHD). In multivariate modeling, incorporation of heart parameters did not significantly improve the fit of RP risk models based on lung parameters alone (p > 0.38 in each case). CONCLUSIONS: In this large clinical cohort, there was no evidence that incidental heart exposure during radiotherapy of NSCLC had a detectable impact on the occurrence of moderate or severe RP.

Analysis of Radiation Therapy Quality Assurance in NRG Oncology RTOG 0848.

PURPOSE: NRG/Radiation Therapy Oncology Group 0848 is a 2-step randomized trial to evaluate the benefit of the addition of concurrent fluoropyrimidine and radiation therapy (RT) after adjuvant chemotherapy (second step) for patients with resected pancreatic head adenocarcinoma. Real-time quality assurance (QA) was performed on each patient who underwent RT. This analysis aims to evaluate adherence to protocol-specified contouring and treatment planning and to report the types and frequencies of deviations requiring revisions. METHODS AND MATERIALS: In addition to a web-based contouring atlas, the protocol outlined step-by-step instructions for generating the clinical treatment volume through the creation of specific regions of interest. The planning target volume was a uniform 0.5 cm clinical treatment volume expansion. One of 2 radiation oncology study chairs independently reviewed each plan. Plans with unacceptable deviations were returned for revision and resubmitted until approved. Treatment started after final approval of the RT plan. RESULTS: From 2014 to 2018, 354 patients were enrolled in the second randomization. Of these, 160 patients received RT and were included in the QA analysis. Resubmissions were more common for patients planned with 3-dimensional conformal RT (43%) than with intensity modulated RT (31%). In total, at least 1 resubmission of the treatment plan was required for 33% of patients. Among patients requiring resubmission, most only needed 1 resubmission (87%). The most common reasons for resubmission were unacceptable deviations with respect to the preoperative gross target volume (60.7%) and the pancreaticojejunostomy (47.5%). CONCLUSION: One-third of patients required resubmission to meet protocol compliance criteria, demonstrating the continued need for expending resources on real-time, pretreatment QA in trials evaluating the use of RT, particularly for pancreas cancer. Rigorous QA is critically important for clinical trials involving RT to ensure that the true effect of RT is assessed. Moreover, RT QA serves as an educational process through providing feedback from specialists to practicing radiation oncologists on best practices.

Pilocytic astrocytoma with leptomeningeal dissemination.

PURPOSE: Pilocytic astrocytoma (PA) is a common pediatric glioma that is generally characterized by indolent growth. However, there are reports of PA disseminating throughout the central nervous system. Given the rarity of dissemination, the appropriate treatment for these patients is poorly defined. In this case series, we describe the clinical characteristics and treatment outcomes of six children treated for disseminated PA at our institution and review the current published literature. METHODS: Six cases of disseminated PA treated at the University of Texas MD Anderson Cancer Center were identified. Demographics, disease characteristics, and follow-up data were compiled. Fifty-three reported cases were identified in the published literature. RESULTS: Our cohort's mean age at presentation was 7 years, and the mean time to identification of disseminated disease was 12 months after initial diagnosis. Two patients underwent chemotherapy, and all underwent proton beam radiation therapy to all or part of the craniospinal axis. With a median follow-up of 24 months after radiation therapy, five of six patients were alive, four with stable disease and one with progressive disease. CONCLUSIONS: Treatment of disseminated PA is frequently multi-modal, including surgical resection, chemotherapy, and radiation therapy. On the basis of early clinical data, extended-field radiation therapy is a viable option for treating disseminated PA.

Contrast-Enhanced Liver Magnetic Resonance Image Synthesis Using Gradient Regularized Multi-Modal Multi-Discrimination Sparse Attention Fusion GAN.

PURPOSES: To provide abdominal contrast-enhanced MR image synthesis, we developed an gradient regularized multi-modal multi-discrimination sparse attention fusion generative adversarial network (GRMM-GAN) to avoid repeated contrast injections to patients and facilitate adaptive monitoring. METHODS: With IRB approval, 165 abdominal MR studies from 61 liver cancer patients were retrospectively solicited from our institutional database. Each study included T2, T1 pre-contrast (T1pre), and T1 contrast-enhanced (T1ce) images. The GRMM-GAN synthesis pipeline consists of a sparse attention fusion network, an image gradient regularizer (GR), and a generative adversarial network with multi-discrimination. The studies were randomly divided into 115 for training, 20 for validation, and 30 for testing. The two pre-contrast MR modalities, T2 and T1pre images, were adopted as inputs in the training phase. The T1ce image at the portal venous phase was used as an output. The synthesized T1ce images were compared with the ground truth T1ce images. The evaluation metrics include peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mean squared error (MSE). A Turing test and experts' contours evaluated the image synthesis quality. RESULTS: The proposed GRMM-GAN model achieved a PSNR of 28.56, an SSIM of 0.869, and an MSE of 83.27. The proposed model showed statistically significant improvements in all metrics tested with p-values < 0.05 over the state-of-the-art model comparisons. The average Turing test score was 52.33%, which is close to random guessing, supporting the model's effectiveness for clinical application. In the tumor-specific region analysis, the average tumor contrast-to-noise ratio (CNR) of the synthesized MR images was not statistically significant from the real MR images. The average DICE from real vs. synthetic images was 0.90 compared to the inter-operator DICE of 0.91. CONCLUSION: We demonstrated the function of a novel multi-modal MR image synthesis neural network GRMM-GAN for T1ce MR synthesis based on pre-contrast T1 and T2 MR images. GRMM-GAN shows promise for avoiding repeated contrast injections during radiation therapy treatment.

Knowledge and Understanding of Radiation Therapy Among Patients With Breast Cancer From Culturally Diverse Backgrounds at a Safety-Net Hospital.

INTRODUCTION: Comprehensive understanding of oncologic treatment is essential for shared decision-making. However, comprehension of information in radiation oncology consults is poorly understood, particularly among Spanish-speaking patients at safetynet hospitals. The purpose of this pilot study was to examine post-consultation radiation oncology knowledge and health literacy among breast cancer patients from culturally diverse backgrounds. METHODS: After consultation for curative post-operative breast radiotherapy (cT1-4N1-3M0), the Radiation Oncology Knowledge Assessment Survey (ROKAS) was administered to Spanish- and English-speaking patients ≥ 18 years old, from January 2021 to January 2022 at a safety-net hospital. Radiation knowledge was assessed using the ROKAS which included eight radiation-specific multiple-choice questions and two separate questions regarding short- and long-term side effects. Additional independent variables included validated questionnaires related to health literacy, health numeracy, acculturation, primary language, and sociodemographic factors. Bivariate Pearson correlations and T-test analyses were conducted to examine the relationship between the independent variables and post-consultation radiation knowledge. RESULTS: Fifty ROKAS were obtained from 25 English- and 25 Spanish-speaking breast cancer patients (median age 57 [IQR 49.75-62.25]). When compared to Englishspeaking patients, Spanish-speaking patients had lower health literacy, health numeracy, and acculturation. There was no difference in the multiple-choice ROKAS score between English- and Spanish-speakers, or correlation with the other independent factors. Higher health numeracy correlated with a higher accuracy for identifying short-term side effects. Lower accuracy of identifying long-term side effects was seen in patients with lower education levels, health literacy, health numeracy, and acculturation, with the most missed long-term side effects being arm swelling, skin toxicity, and heart toxicity. CONCLUSIONS: Patients with low health literacy, health numeracy, acculturation, and education levels as well as Spanish-speaking patients were associated with poor understanding of radiotherapy long-term side effects. Determining barriers to radiation knowledge is crucial to improve shared decision-making between patients and providers in a culturally diverse population.

Racial disparities and standard treatment in locally advanced rectal cancer: a National Cancer Database study.

Background: Mortality rates in colorectal cancer (CRC) continue to be higher in Black compared to White patients. While standard treatment modalities for locally advanced rectal cancer have been shown to improve outcomes, there are limited studies assessing the receipt of standard treatment in rectal cancer based on race. Therefore, we sought to evaluate the use of standard treatment across racial groups in locally advanced rectal cancer and its effect on survival. Methods: The National Cancer Database (NCDB) was queried for patients ≥18 years old with clinical and pathologic stage II-III rectal adenocarcinoma who received treatment from 2004 to 2014. Standard treatment was defined as complete surgical excision with either neoadjuvant or adjuvant concurrent chemoradiation. Multivariable logistic regressions were used to identify racial differences in receiving standard treatment. Cox proportional hazards were used to estimate the effects of standard vs. nonstandard treatment on survival differences based on race. Results: A total of 70,677 patients with stage II (n=35,079) or stage III (n=35,598) rectal adenocarcinoma met the inclusion criteria. On multivariate analysis, Black [odds ratio (OR): 0.75; 95% confidence interval (CI): 0.71-0.79; P<0.001] and Hispanic White (OR: 0.86; 95% CI: 0.80-0.92; P>0.001) patients were less likely to receive standard treatment compared to non-Hispanic White patients. On multivariable Cox regression, nonstandard treatment was significantly associated with worse survival [hazard ratio (HR): 1.69; 95% CI: 1.65-1.73; P<0.001] compared to standard treatment. Even after adjusting for patient, demographic, and facility characteristics, Black patients had higher mortality rates compared to White patients in the whole population (HR: 1.15; 95% CI: 1.09-1.20; P<0.0001). This survival difference between Black and non-Hispanic White patients persisted in both the standard (HR: 1.10; 95% CI: 1.03-1.19; P=0.008) and nonstandard (HR: 1.17; 95% CI: 1.10-1.25; P<0.0001) treatment subgroups. Decreased survival outcomes in Black patients were more pronounced for those who underwent nonstandard treatment, particularly when treating stage III disease (HR: 1.30; 95% CI: 1.19-1.42; P<0.0001). Conclusions: Nonstandard treatment in stage II and III rectal cancer is associated with worse survival compared to standard treatment regimens. Black patients are more likely to receive nonstandard treatment and have worse survival outcomes compared to White patients.

Automatic segmentation of high-risk clinical target volume for tandem-and-ovoids brachytherapy patients using an asymmetric dual-path convolutional neural network.

PURPOSES: Preimplant diagnostic magnetic resonance imaging is the gold standard for image-guided tandem-and-ovoids (T&O) brachytherapy for cervical cancer. However, high dose rate brachytherapy planning is typically done on postimplant CT-based high-risk clinical target volume (HR-CTVCT ) because the transfer of preimplant Magnetic resonance (MR)-based HR-CTV (HR-CTVMR ) to the postimplant planning CT is difficult due to anatomical changes caused by applicator insertion, vaginal packing, and the filling status of the bladder and rectum. This study aims to train a dual-path convolutional neural network (CNN) for automatic segmentation of HR-CTVCT on postimplant planning CT with guidance from preimplant diagnostic MR. METHODS: Preimplant T2-weighted MR and postimplant CT images for 65 (48 for training, eight for validation, and nine for testing) patients were retrospectively solicited from our institutional database. MR was aligned to the corresponding CT using rigid registration. HR-CTVCT and HR-CTVMR were manually contoured on CT and MR by an experienced radiation oncologist. All images were then resampled to a spatial resolution of 0.5 × 0.5 × 1.25 mm. A dual-path 3D asymmetric CNN architecture with two encoding paths was built to extract CT and MR image features. The MR was masked by HR-CTVMR contour while the entire CT volume was included. The network put an asymmetric weighting of 18:6 for CT: MR. Voxel-based dice similarity coefficient (DSCV ), sensitivity, precision, and 95% Hausdorff distance (95-HD) were used to evaluate model performance. Cross-validation was performed to assess model stability. The study cohort was divided into a small tumor group (<20 cc), medium tumor group (20-40 cc), and large tumor group (>40 cc) based on the HR-CTVCT for model evaluation. Single-path CNN models were trained with the same parameters as those in dual-path models. RESULTS: For this patient cohort, the dual-path CNN model improved each of our objective findings, including DSCV , sensitivity, and precision, with an average improvement of 8%, 7%, and 12%, respectively. The 95-HD was improved by an average of 1.65 mm compared to the single-path model with only CT images as input. In addition, the area under the curve for different networks was 0.86 (dual-path with CT and MR) and 0.80 (single-path with CT), respectively. The dual-path CNN model with asymmetric weighting achieved the best performance with DSCV of 0.65 ± 0.03 (0.61-0.70), 0.79 ± 0.02 (0.74-0.85), and 0.75 ± 0.04 (0.68-0.79) for small, medium, and large group. 95-HD were 7.34 (5.35-10.45) mm, 5.48 (3.21-8.43) mm, and 6.21 (5.34-9.32) mm for the three size groups, respectively. CONCLUSIONS: An asymmetric CNN model with two encoding paths from preimplant MR (masked by HR-CTVMR ) and postimplant CT images was successfully developed for automatic segmentation of HR-CTVCT for T&O brachytherapy patients.

Racial disparities in receipt of standard chemoradiation in anal squamous cell carcinoma, an analysis of the National Cancer Database.

BACKGROUND: Standard treatment for locally advanced anal squamous cell carcinoma (SCC) consists of concurrent chemoradiation. We evaluated whether racial differences exist in the receipt of standard treatment and its association with survival. METHODS: From the National Cancer Database, we identified patients diagnosed with anal SCC (Stages 2-3) between 2004 and 2015. Using logistic regression, we evaluated racial differences in the probability of receiving standard chemoradiation. We used Cox proportional hazards models to evaluate associations between race, receipt of standard therapy and survival. RESULTS: Our analysis included 19,835 patients. Patients receiving standard chemoradiation had better survival than patients receiving nonstandard therapy (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61-0.68; p < 0.001). Compared to White patients, Black patients were less likely to receive standard therapy (odds ratio [OR] 0.85; 95% CI 0.76-0.96; p < 0.008). We observed no statistical difference in mortality between Black and White patients overall (HR 1.05, 95% CI 0.97-1.15; p = 0.24). However, for the subgroup of patients receiving nonstandard therapy, Black patients had an increased mortality risk compared to White patients (HR 1.17, CI 1.01-1.35; p = 0.034). We observed no survival differences in the subgroup of patients receiving standard treatment (HR 1.00, CI 0.90-1.11, p = 0.99). CONCLUSION: Standard treatment in anal SCC is associated with better survival, but Black patients are less likely to receive standard treatment than White patients. Although Black patients had higher mortality than White patients in the subgroup of patients receiving nonstandard therapy, this difference was ameliorated in the subset receiving standard therapy.

Acral lentiginous melanoma-Population, treatment, and survival using the NCDB from 2004 to 2015.

Acral lentiginous melanoma (ALM) is a rare histological subtype of cutaneous malignant melanoma that typically presents on the palms and soles. To characterize the demographic and treatment characteristics of ALM, we used the National Cancer Database (NCDB) to describe a large multi-institutional cohort of ALM patients, consisting of 4,796 ALM patients from 2004 to 2015. ALM was more likely to be diagnosed at a later stage overall compared with non-ALM cutaneous melanomas, and more likely to be thicker, ulcerated, lymph node positive, and have lymphovascular invasion and positive margins. When stratified by stage, ALM had worse survival compared with non-ALM patients, most notably in stage III patients with 5-year survival of 47.5% versus 56.7%, respectively (p < .001). In ALM patients, older age, male sex, higher comorbidity burden, increased tumor thickness and ulceration, positive lymph nodes, and positive metastasis were independently associated with lower 5-year survival. Multimodality therapy, defined as surgery in addition to systemic therapy and/or radiation therapy, was associated with higher survival in stage III patients but not in other stages. These results call for further investigation into possible treatment intensification in the ALM population in the future.

Use of Salvage Surgery or Stereotactic Radiosurgery for Multiply Recurrent Skull Base Chordomas: A Single-Institution Experience and Review of the Literature.

Introduction Chordomas are locally destructive neoplasms characterized by appreciable recurrence rates after initial multimodality treatment. We examined the outcome of salvage treatment in recurrent/progressive skull base chordomas. Methods This is a retrospective review of recurrent/progressive skull base chordomas at a tertiary urban academic medical center. The outcomes evaluated were overall survival, progression-free survival (PFS), and incidence of new toxicity. Results Eighteen consecutive patients who underwent ≥1 course of treatment (35.3% salvage surgery, 23.5% salvage radiation, and 41.2% both) were included. The median follow-up was 98.6 months (range 16-215 months). After initial treatment, the median PFS was 17.7 months (95% confidence interval [CI]: 4.9-22.6 months). Following initial therapy, age ≥ 40 had improved PFS on univariate analysis ( p = 0.03). All patients had local recurrence, with 15 undergoing salvage surgical resections and 16 undergoing salvage radiation treatments (mostly stereotactic radiosurgery [SRS]). The median PFS was 59.2 months (95% CI: 4.0-99.3 months) after salvage surgery, 58.4 months (95% CI: 25.9-195 months) after salvage radiation, and 58.4 months (95% CI: 25.9.0-98.4 months) combined. Overall survival for the total cohort was 98.7% ± 1.7% at 2 years and 92.8% ± 5.5% at 5 years. Salvage treatments were well-tolerated with two patients (11%) reporting tinnitus and one patient each (6%) reporting headaches, visual field deficits, hearing loss, anosmia, dysphagia, or memory loss. Conclusion Refractory skull base chordomas present a challenging treatment dilemma. Repeat surgical resection or SRS seems to provide adequate salvage therapy that is well-tolerated when treated at a tertiary center offering multimodality care.

Automatic detection and segmentation of multiple brain metastases on magnetic resonance image using asymmetric UNet architecture.

Detection of brain metastases is a paramount task in cancer management due both to the number of high-risk patients and the difficulty of achieving consistent detection. In this study, we aim to improve the accuracy of automated brain metastasis (BM) detection methods using a novel asymmetric UNet (asym-UNet) architecture. An end-to-end asymmetric 3D-UNet architecture, with two down-sampling arms and one up-sampling arm, was constructed to capture the imaging features. The two down-sampling arms were trained using two different kernels (3 × 3 × 3 and 1 × 1 × 3, respectively) with the kernel (1 × 1 × 3) dominating the learning. As a comparison, vanilla single 3D UNets were trained with different kernels and evaluated using the same datasets. Voxel-based Dice similarity coefficient (DSCv), sensitivity (S v), precision (P v), BM-based sensitivity (S BM), and false detection rate (F BM) were used to evaluate model performance. Contrast-enhanced T1 MR images from 195 patients with a total of 1034 BMs were solicited from our institutional stereotactic radiosurgery database. The patient cohort was split into training (160 patients, 809 lesions), validation (20 patients, 136 lesions), and testing (15 patients, 89 lesions) datasets. The lesions in the testing dataset were further divided into two subgroups based on the diameters (small S = 1-10 mm, large L = 11-26 mm). In the testing dataset, there were 72 and 17 BMs in the S and L sub-groups, respectively. Among all trained networks, asym-UNet achieved the highest DSCv of 0.84 and lowest F BM of 0.24. Although vanilla 3D-UNet with a single 1 × 1 × 3 kernel achieved the highest sensitivities for the S group, it resulted in the lowest precision and highest false detection rate. Asym-UNet was shown to balance sensitivity and false detection rate as well as keep the segmentation accuracy high. The novel asym-UNet segmentation network showed overall competitive segmentation performance and more pronounced improvement in hard-to-detect small BMs comparing to the vanilla single 3D UNet.

Competing with a pandemic: Trends in research design in a time of Covid-19.

INTRODUCTION: During the Covid-19 pandemic, major journals have published a significant number of Covid-19 related articles in a short period of time. While this is necessary to combat the worldwide pandemic, it may have trade-offs with respect to publishing research from other disciplines. OBJECTIVES: To assess differences in published research design before and after the Covid-19 pandemic. METHODS: We performed a cross-sectional review of all 322 full-length research studies published between October 1, 2019 and April 30, 2020 in three major medical journals. We compared the number of randomized controlled trials (RCTs) and studies with a control group before and after January 31, 2020, when Covid-19 began garnering international attention. RESULTS: The number of full-length research studies per issue was not statistically different before and after the Covid-19 pandemic (from 3.7 to 3.5 per issue, p = 0.17). Compared to before January 31, 2020, 0.7 fewer non-Covid-19 studies per issue were published versus after January 31, 2020 (p<0.001), a change that was offset by Covid-19 studies. Among non-Covid-19 studies, 0.9 fewer studies with a control group per issue were published after January 31, 2020, with RCTs contributing to nearly all the decline (p<0.001, p = 0.001, respectively). In the same timeframe, non-Covid-19 studies without a control group and non-Covid-19 studies without randomization experienced relatively small changes that did not meet our threshold for statistical significance (increases of 0.1 and 0.1 per issue, p = 0.80, p = 0.88, respectively). LIMITATIONS: Using a simple heuristic for assessing research design and lack of generalizability to the general medical literature. CONCLUSIONS: In summary, the increase in Covid-19 studies coincided with a decrease of mostly non-Covid-19 RCTs.

Cost-effectiveness of chemoradiation followed by esophagectomy versus chemoradiation alone in squamous cell carcinoma of the esophagus.

BACKGROUND: Standard treatment for locally advanced esophageal cancer usually includes a combination of chemotherapy, radiation, and surgery. In squamous cell carcinoma (SCC), recent studies have indicated that esophagectomy after chemoradiation does not significantly improve survival but may reduce recurrence at the cost of treatment-related mortality. This study aims to evaluate the cost-effectiveness of chemoradiation with and without esophagectomy. METHODS: We developed a decision tree and Markov model to compare chemoradiation therapy alone (CRT) versus chemoradiation plus surgery (CRT+S) in a cohort of 57-year-old male patients with esophageal SCC, over 25 years. We used information on survival, cancer recurrence, and side effects from a Cochrane meta-analysis of two randomized trials. Societal utility values and costs of cancer care (2017, USD) were from medical literature. To test robustness, we conducted deterministic (DSA) and probabilistic sensitivity analyses (PSA). RESULTS: In our base scenario, CRT resulted in less cost for more quality-adjusted life years (QALYs) compared to CRT+S ($154 082 for 1.32 QALYs/patient versus $165 035 for 1.30 QALYs/patient, respectively). In DSA, changes resulted in scenarios where CRT+S is cost-effective at thresholds between $100 000-$150 000/QALY. In PSA, CRT+S was dominant 17.9% and cost-effective at willingness-to-pay of $150 000/QALY 38.9% of the time, and CRT was dominant 30.6% and cost-effective 61.1% of the time. This indicates that while CRT would be preferred most of the time, variation in parameters may change cost-effectiveness outcomes. CONCLUSIONS: Our results suggest that more data is needed regarding the clinical benefits of CRT+S for treatment of localized esophageal SCC, although CRT should be cautiously preferred.

Quantifying vascular invasion in pancreatic cancer-a contrast CT based method for surgical resectability evaluation.

Pancreatic cancer (PC) is one of the most lethal cancers, with frequent local therapy resistance and dismal 5-year survival rate. To date, surgical resection remains to be the only treatment option offering potential cure. Unfortunately, at diagnosis, the majority of patients demonstrate varying levels of vascular infiltration, which can contraindicate surgical resection. Patients unsuitable for immediate resection are further divided into locally advanced (LA) and borderline resectable (BR), with different treatment goals and therapeutic designs. Accurate definition of resectability is thus critical for PC patients, yet the existing methods to determine resectability rely on descriptive abutment to surrounding vessels rather than quantitative geometric characterization. Here, we aim to introduce a novel intra-subject object-space support-vector-machine (OsSVM) method to quantitatively characterize the degree of vascular involvement-the main factor determining the PC resectability. Intra-subject OsSVMs were applied on 107 contrast CT scans (56 LA, BR and 26 resectable (RE) PC cases) for optimized tumor-vessel separations. Nine metrics derived from OsSVM margins were calculated as indicators of the overall vascular infiltration. The combined sets of matrics selected by the elastic net yielded high classification capability between LA and BR (AUC = 0.95), as well as BR and RE (AUC = 0.98). The proposed OsSVM method may provide an improved quantitative imaging guideline to refine the PC resectability grading system.

Combination ipilimumab and radiosurgery for brain metastases: tumor, edema, and adverse radiation effects.

OBJECTIVETumor and edema volume changes of brain metastases after stereotactic radiosurgery (SRS) and ipilimumab are not well described, and there is concern regarding the safety of combination treatment. The authors evaluated tumor, edema, and adverse radiation-induced changes after SRS with and without ipilimumab and identified associated risk factors.METHODSThis single-institution retrospective study included 72 patients with melanoma brain metastases treated consecutively with upfront SRS from 2006 to 2015. Concurrent ipilimumab was defined as ipilimumab treatment within 4 weeks of SRS. At baseline and during each follow-up, tumor and edema were measured in 3 orthogonal planes. The (length × width × height/2) formula was used to estimate tumor and edema volumes and was validated in the present study for estimation of edema volume. Tumor and edema volume changes from baseline were compared using the Kruskal-Wallis test. Local failure, lesion hemorrhage, and treatment-related imaging changes (TRICs) were analyzed with the Cox proportional hazards model.RESULTSOf 310 analyzed lesions, 91 were not treated with ipilimumab, 59 were treated with concurrent ipilimumab, and 160 were treated with nonconcurrent ipilimumab. Of 106 randomly selected lesions with measurable peritumoral edema, the mean edema volume by manual contouring was 7.45 cm3 and the mean volume by (length × width × height)/2 formula estimation was 7.79 cm3 with R2 = 0.99 and slope of 1.08 on line of best fit. At 6 months after SRS, the ipilimumab groups had greater tumor (p = 0.001) and edema (p = 0.005) volume reduction than the control group. The concurrent ipilimumab group had the highest rate of lesion response and lowest rate of lesion progression (p = 0.002). Within the concurrent ipilimumab group, SRS dose ≥ 20 Gy was associated with significantly greater median tumor volume reduction at 3 months (p = 0.01) and 6 months (p = 0.02). The concurrent ipilimumab group also had the highest rate of lesion hemorrhage (p = 0.01). Any ipilimumab was associated with higher incidence of symptomatic TRICs (p = 0.005). The overall incidence of pathologically confirmed radiation necrosis (RN) was 2%. In multivariate analysis, tumor and edema response at 3 months were the strongest predictors of local failure (HR 0.131 and HR 0.125) and lesion hemorrhage (HR 0.225 and HR 0.262). Tumor and edema response at 1.5 months were the strongest predictors of TRICs (HR 0.144 and HR 0.297).CONCLUSIONSThe addition of ipilimumab improved tumor and edema volume reduction but was associated with a higher incidence of lesion hemorrhage and symptomatic TRICs. There may be a radiation dose-response relationship between SRS and ipilimumab when administered concurrently. Early tumor and edema response were excellent predictors of subsequent local failure, lesion hemorrhage, and TRICs. The incidence of pathologically proven RN was low, supporting the relative safety of ipilimumab in radiosurgery treatment.

The growing importance of lesion volume as a prognostic factor in patients with multiple brain metastases treated with stereotactic radiosurgery.

Stereotactic Radiosurgery (SRS) is considered standard of care for patients with 1-3 brain metastases (BM). Recent observational studies have shown equivalent OS in patients with 5+ BM compared to those with 2-4, suggesting SRS alone may be appropriate in these patients. We aim to review outcomes of patients treated with SRS with 2-4 versus 5+ BM. This analysis included consecutive patients from 1994 to 2015 treated with SRS. Of 1017 patients, we excluded patients with a single BM and patients without adequate survival data, resulting in 391 patients. All risk factors were entered into univariate analysis using Cox proportional hazards model, and significant factors were entered into multivariate analysis (MVA). We additionally analyzed outcomes after excluding patients with prior surgery or whole-brain radiotherapy (WBRT). Median follow-up was 7.1 months. Median KPS was 90, mean age was 59, and most common histologies were melanoma and lung. Median tumor volume was 3.41 cc. Patients with 2-4 BM had a median OS of 8.1 months compared to 6.2 months for those with 5+ BM (P = 0.0136). On MVA, tumor volume, KPS, and histology remained significant for OS, whereas lesion number did not. Similar results were found when excluding patients with prior surgery or WBRT. Rather than lesion number, the strongest prognostic factors for patients undergoing SRS were tumor volume >10 cc, KPS, and histology. BM number may therefore not be the most important criterion for candidacy for SRS. Patients with 5 or more BM should be considered for SRS.

Percent of Tracer Clearance at 40 Minutes in MAG3 Renal Scans Is More Sensitive Than T1/2 for Symptomatic Ureteropelvic Junction Obstruction.

OBJECTIVE: To increase the diagnostic sensitivity of standard MAG3 diuretic renal scans for ureteropelvic junction obstruction (UPJO) by exploring the utility of an alternative measurement P40, the percentage of maximal tracer counts present at 40 minutes. MATERIALS AND METHODS: Patients with strong clinical and anatomic evidence for UPJO may have a normal T1/2, making definitive diagnosis difficult. We reviewed the charts of 142 consecutive patients who underwent successful laparoscopic or robotic-assisted laparoscopic pyeloplasty for UPJO between 2005 and 2015. Both pre- and postoperative renal scan images were available for 37 symptomatic patients with primary unilateral UPJO and 2 kidneys. We defined P40 as the percentage of maximal tracer counts present at 40 minutes. We identified the upper limit of normal (97.5th percentile, +2SD) for P40 using the preoperative renal scans from the unaffected kidney. We compared the sensitivity of P40 to T1/2 to identify symptomatic UPJO. RESULTS: In our cohort, 51% of symptomatic patients (n = 19) had a normal T1/2 (median 8.9 minutes; interquartile range: 7.5 minutes) and 49% (n = 18) had an abnormal T1/2 (median: 40 minutes; interquartile range: 0 minute). None of the patients had an abnormal P40 on their unaffected kidney. All patients with an abnormal T1/2 also had an abnormal P40. P40 increased the sensitivity of the renal scan from 49% (n = 18 of 37) to 73% (n = 27 of 37) when compared to T1/2. The majority of patients (95%) demonstrated an improvement in P40 after pyeloplasty. CONCLUSION: P40 markedly increases the sensitivity of a renal scan for diagnosing symptomatic UPJO and may be another valuable marker in addition to T1/2 to document functional improvement in drainage after pyeloplasty.