Primary Malignancy Research Articles

Outcomes with initiation of inpatient immunotherapy.

7 Background: Immune checkpoint inhibitors (ICIs) have transformed cancer care; however, studies establishing their benefit have been primarily conducted in robust patients (pts) with good performance status. Administration of ICI to hospitalized pts remains a subject of debate. While there is often a desire to reverse clinical course in patients who are acutely ill, previous studies show minimal benefit from anticancer therapy near the end of life with the potential for toxicity. While ICI are generally better tolerated than traditional cancer therapies, the median time to response ranges from 2-6 months and pts with a poor PS may not derive benefit. ICIs also bring significant financial burdens to pts and healthcare systems. The role of ICIs in the inpatient setting remains unclear. Methods: This study retrospectively examined pts who received PD-(L)1 inhibitors while IP between 2016 and 2023 at MedStar Georgetown University Hospital. Data were collected manually from institutional EMR. Descriptive statistics were used to depict the pt population and show their outcomes. The Kaplan-Meier method estimated survival probabilities from treatment initiation to follow-up or death, with 95% confidence intervals (α = 0.05). The Log rank non-parametric test compared survival distributions among ICIs. Results: Of the 38 pts who initiated ICI as an inpatient, 16 were male (42.1%) and 22 were female (57.9%). The median age was 60 years (31–88 years). Gastrointestinal malignancies were most common indication (31.6%), followed by thoracic/head and neck (21.1%) and hematologic (18.4%) cancers. Among the cohort, 26.3% received nivolumab, 68.4% received pembrolizumab, and 5.3% received a combination of nivolumab and ipilimumab. PD-L1 status was unknown for the majority (79.0%) of pts at time of ICI; 15.8 % were known to be PD-L1 high. Only 14 of 35 (40.0%) patients went on to receive any additional immunotherapy after discharge. The median days to death after discharge was 16 days (0-376 days), with a mean of 36.4 days. The median overall survival was 137 days from IP treatment initiation. The survival probability at 91 days was 65.5% (95% CI: 45.4-79.7) and 31.0% (95% CI: 15.6-47.9) at 182 days. No significant differences were observed between the survival distributions by ICI type (p=0.966) or primary malignancy (p=0.488). Conclusions: Our findings underscore the complexities of initiating inpatient ICI treatment and question its appropriateness. Delaying ICI to outpatient settings may enhance pt tolerance, optimize outcomes, and potentially mitigate unnecessary costs. This approach may allow thorough consideration of performance status outside the hospital, possibly improving treatment effectiveness while reducing futile acute care costs.

Using artificial intelligence based imaging to predict lymph node metastasis in non-small cell lung cancer: a systematic review and meta-analysis.

Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most-deadly malignancies worldwide. Lung cancer has a worse 5-year survival rate than many primary malignancies. Thus, the early detection and prognosis prediction of lung cancer are crucial. The early detection and prognosis prediction of lung cancer have improved with the widespread use of artificial intelligence (AI) technologies. This meta-analysis examined the accuracy and efficacy of AI-based models in predicting lymph node metastasis (LNM) in NSCLC patients using imaging data. Our findings could help clinicians predict patient prognosis and select alternative therapies. We searched the PubMed, Web of Science, Cochrane Library, and Embase databases for relevant articles published up to January 31, 2024. Two reviewers individually evaluated all the retrieved articles to assess their eligibility for inclusion in the meta-analysis. The systematic assessment and meta-analysis comprised articles that satisfied the inclusion criteria (e.g., randomized or non-randomized trials, and observational studies) and exclusion criteria (e.g., articles not published in English), and provided data for the quantitative synthesis. The quality of the included articles was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The pooled sensitivity, specificity, and area under the curve (AUC) were used to evaluate the ability of AI-based imaging models to predict LNM in NSCLC patients. Sources of heterogeneity were investigated using meta-regression. Covariates, including country, sample size, imaging modality, model validation technique, and model algorithm, were examined in the subgroup analysis. The final meta-analysis comprised 11 retrospective studies of 6,088 NSCLC patients, of whom 1,483 had LNM. The pooled sensitivity, specificity, and AUC of the AI-based imaging model for predicting LNM in NSCLC patients were 0.87 [95% confidence interval (CI): 0.80-0.91], 0.85 (95% CI: 0.78-0.89), and 0.92 (95% CI: 0.90-0.94). Based on the QUADAS-2 results, a risk of bias was detected in the patient selection and diagnostic tests of the included articles. However, the quality of the included articles was generally acceptable. The pooled sensitivity and specificity were heterogeneous (I2>75%). The meta-regression and subgroup analyses showed that imaging modality [computed tomography (CT) or positron emission tomography (PET)/CT], and the neural network method model design significantly affected heterogeneity of this study. Models employing sample size data from a single center and the least absolute shrinkage and selection operator (LASSO) method had greater sensitivity than other techniques. Using the Deek' s funnel plot, no publishing bias was found. The results of the sensitivity analysis showed that deleting each article one by one did not change the findings. Imaging data models based on AI algorithms have good diagnostic accuracy in predicting LNM in patients with NSCLC and could be applied in clinical settings.

Relationship between self-reported challenges with social determinants of health and delayed time-to-treatment initiation for gynecologic malignancies.

90 Background: Delays in time to treatment initiation (TTI) for gynecologic malignancies have been associated with worse survival. Worsened outcomes and presentation with more advanced disease are more common for gynecologic cancer patients who come from socioeconomically disadvantaged populations and whose healthcare is negatively impacted by their social determinants of health (SDoH). There is a need to characterize the particular social determinants of health that are associated with delays in treatment initiation in patients with gynecologic malignancy, particularly in underserved urban populations. Methods: Retrospective cohort study at an urban community-based academic center. Participants were 257 patients with primary gynecologic malignancy either of the cervix, ovary, uterus, vulva/vagina or NOS diagnosed between January 2017 and August 2022, identified through the Montefiore Medical Center Cancer Registry. The primary exposure was TTI, defined as the duration between histopathological diagnosis and initial treatment. Univariate and multivariate logistic regression analyses were conducted to examine the association between delays in TTI and SDoH. Multivariate Cox proportional hazard regression was used to obtain hazard ratios and 95% confidence intervals associated with TTI. Results: Among 257 patients with gynecologic malignancy (median [IQR] age 63 [56-72] years), 205 patients were treated within 45 days of diagnosis, and 52 were treated at or after 45 days. Predictors of delayed TTI (defined as ≥45 days) included positive SDoH screening in univariate logistic regression (OR = 3.12, 95% CI 1.39-6.98, p = 0.0061) and in multivariate logistic regression (OR = 3.06, 95% CI 2.62-3.57, p<0.001) as well as increased age in multivariate logistic regression (OR = 1.02, 95% CI 1.02-1.03, p<0.001). Multivariate logistic regression showed that protective factors for delayed TTI were Non-Hispanic Black race/ethnicity (OR = 0.87, 95% CI 0.77-0.99, p = 0.0351), non-Hispanic white race/ethnicity (OR = 0.37, 95% CI 0.30-0.46, p<0.001), inpatient stay within 30 days of diagnosis (OR = 0.74, 95% CI 0.62-0.88, p=0.001) and AJCC clinically late stage (OR = 0.57, 95% CI 0.50-0.66, p<0.001). Conclusions: In patients with gynecologic malignancies, greater SDoH burden increases risk for delays in treatment ≥ 45 days from diagnosis. Non-Hispanic race/ethnicity, inpatient stay within 30 days of diagnosis and clinically late-stage diagnoses are protective factors for expedited treatment initiation. Identification of predictive and protective factors for treatment delay will help identify at-risk patients and facilitate earlier intervention in hospitals with underserved populations.

Evaluation of lymph node ratios and log odds of positive nodes as prognostic indicators in primary organ malignancy

BackgroundStaging of malignant tumours based on positive lymph node number and not taking into account the actual number of examined lymph nodes during surgery may lead to bias and fallacious results. The ratio of positive and resected lymph nodes (LNR) and log odds of positive nodes (LODDS) emerged as novel prognostic markers in deciding the future course of management better than the parameter pN in predicting cancer-specific survival. We aim to evaluate and compare the prognostic value of pN, LNR and LODDS in common primary organ malignancies like breast, head and neck, gastric and cervical cancers. MethodsThis was an ambidirectional observational study conducted from September 2018 to August 2021 with one year (from 2017 to 2018) for retrospective data collection archived from records. It included patients affected by breast, head and neck, gastric and cervical cancers and were followed up for a period of 3 years from the date of diagnosis to perform a holistic survival analysis. The sample was grouped by American Joint Committee on Cancer N stage, LNR and LODDS, and analysed using Kaplan–Meier and multivariate Cox proportional hazard models. ResultsThe study included 202 breast cancer patients, 85 head and neck cancer patients, 100 gastric cancer patients and 52 cervical cancer patients. Multivariate Cox regressions analysis demonstrated a lower Akaike Information Criterion (AIC) value for LODDS and LNR followed by pN stage. ConclusionThe novel indicators LNR and LODDS better predicted the biological behaviour irrespective of lymph node number and allowed clinicians to correctly stratify patients for better postoperative management.

S2939 High-Grade Urothelial Carcinoma Presenting as a Rectosigmoid Mass: An Unusual Mimicker of a Primary Colorectal Malignancy

S2939 High-Grade Urothelial Carcinoma Presenting as a Rectosigmoid Mass: An Unusual Mimicker of a Primary Colorectal Malignancy

Osteosarcoma and Langerhans Cell Histiocytosis in a Pediatric Patient with Lynch Syndrome: A Case Report.

Lynch syndrome (hereditary nonpolyposis colorectal cancer) is associated with extracolonic manifestations, but skeletal tumors are rare. Our patient, a 12-year-old boy with Lynch syndrome, developed osteosarcoma of the left femur. Treatment included cytotoxic chemotherapy, wide resection, and pembrolizumab. Two years later, he developed an aggressive lesion in the contralateral femur that was thought to be metastatic osteosarcoma but which histology revealed to be Langerhans cell histiocytosis. This case underscores the importance of advanced testing in patients with osteosarcoma and poor response to chemotherapy, and of tissue sampling when patients with a primary malignancy develop new bone lesions. IV.

Efficient application of deep learning-based elective lymph node regions delineation for pelvic malignancies.

While there are established international consensuses on the delineation of pelvic lymph node regions (LNRs), significant inter- and intra-observer variabilities persist. Contouring these clinical target volumes for irradiation in pelvic malignancies is both time-consuming and labor-intensive. The purpose of this study was to develop a deep learning model of pelvic LNRs delineation for patients with pelvic cancers. Planning computed tomography (CT) studies of 160 patients with pelvic primary malignancies (including rectal, prostate, and cervical cancer) were retrospectively collected and divided into training set (n=120) and testing set (n=40). Six pelvic LNRs, including abdominal presacral, pelvic presacral, internal iliac nodes, external iliac nodes, obturator nodes, and inguinal nodes were delineated by two radiation oncologists as ground truth (Gt) contours. The cascaded multi-heads U-net (CMU-net) was constructed based on the Gt contours from training cohort, which was subsequently verified in the testing cohort. The automatic delineation of six LNRs (Auto) was evaluated using dice similarity coefficient (DSC), average surface distance (ASD), 95th percentile Hausdorff distance (HD95), and a 7-point scale score. In the testing set, the DSC of six pelvic LNRs by CMU-net model varied from 0.851 to 0.942, ASD from 0.381 to 1.037mm, and HD95 from 2.025 to 3.697mm. No significant differences were founded in these three parameters between postoperative and preoperative cases. 95.9% and 96.2% of auto delineations by CMU-net model got a score of 1-3 by two expert radiation oncologists, respectively, meaning only minor edits needed. The CMU-net was successfully developed for automated delineation of pelvic LNRs for pelvic malignancies radiotherapy with improved contouring efficiency and highly consistent, which might justify its implementation in radiotherapy work flow.

Most common primary malign embriological tumor: a case report

Most common primary malign embriological tumor: a case report

General versus disease-specific medical oncology consults and impact on inpatient quality of care.

321 Background: Hospitalization is a time of crisis for patients and caregivers. Subspeciality oncologists may bring more timely, effective support compared to a general oncologists. Attendings, fellows and advance practice providers (APPs) may benefit from focused expertise for consultative care and education. Methods: Subspeciality oncology consults launched July 2023, with consults staffed by 4 oncologists from: 1) breast 2) head and neck/thoracic 3) gastrointestinal and 4) genitourinary/melanoma. Previously, 3 oncologists staffed all patients, regardless of primary malignancy. Throughout the study period, oncologists were supported by at least 1 fellow or 1 APP. Using Epic and Tableau, we collected LOS, time to consult (TTC), ICU rate, hospice referral rate, 30-day readmission, 30-day emergency department (ED) visit data. Using Qualtrics, we collected fellow, attending, and APP satisfaction feedback pre- and post-intervention. Data was analyzed using R-4.40. Oncologists, fellows, and APPs completed Qualtrics surveys pre- and post-intervention regarding their experience. Results: Subspeciality oncology consults were associated with a significant decrease in LOS, TTC, and ICU rate. Median LOS decreased by 2.0 days (P<0.001), with median TTC decreasing by 1.0 hour (P=0.003). ICU rate decreased from 27.5% to 16.4% (P<0.001). There was no difference in hospice referrals or 30-day ED visits. A significant increase in 30-day readmission during post-intervention was observed (Table). Oncologists reported a high level of satisfaction with the program. Oncologist, fellow, and APP overall experience and educational rankings increased after the introduction of subspeciality consults. Inpatient productivity measured by wRVU increased by 30% following the intervention, without associated changes to outpatient productivity. Conclusions: Transition to a subspeciality oncology consult model improved inpatient quality of care, as well as clinician experience. Additionally, inpatient productivity increased without decrease in outpatient metrics. Subspeciality medical oncology consultation can improve inpatient quality of care, education, clinician satisfaction and productivity. Subspeciality oncology consult outcomes. General Consults (Baseline)* Subspeciality Consults (Intervention) P-value Median TTC (Hours) 4.0 (1.5-6.0)** 3.0 (0-5.0)** P=0.003 Median LOS (Days) 7.0 (4.0-13.0)** 5.0 (3.0-10.0)** P<0.001 ICU Rate 148 (27.5%) 161 (16.4%) P<0.001 Hospice Referral Rate 56 (10.4%) 95 (9.7%) 0.655 30-Day Readmission Rate 136 (25.3%) 301 (30.7%) 0.028 30-Day ED Rate 157 (29.2%) 315 (32.1%) 0.247 *Baseline data reflects outcomes for general oncology consult staffing, prior to initiation of subspeciality consult model (pre-intervention). **Interquartile Range (IQR).

Chronic Invasive Fungal Sinusitis Mimicking Malignancy Post-Radiotherapy: A Case Report.

Invasive fungal sinusitis is a life-threatening form of fungal rhinosinusitis. Due to the aggressive clinical presentation and radiological appearance, there is diagnostic difficulty in differentiating invasive fungal sinusitis from a malignant process. This is even more challenging in oncological patients who have undergone previous head and neck radiotherapy, due to possibility of a recurrence of primary malignancy and radiation-induced neoplasms. We report a rare case of invasive fungal sinusitis mimicking a malignancy in a post-radiotherapy patient.Our patient was a 68-year-old male, 25-years post-radiotherapy for nasopharyngeal carcinoma. He presented with a 3-month history of purulent sputum and right facial paraesthesia. Magnetic resonance imaging showed an irregular destructive enhancing mass of the greater wing of right sphenoid and pterygoid bone with extensive extension into nearby structures. In view of extensive local and bony invasion, and a history of radiotherapy, initial suspicions were that of primary malignancy, specifically radiation-induced sarcoma, and recurrence of nasopharyngeal carcinoma. He underwent transpterygoid biopsy of the lesion, and histopathology demonstrated Aspergillus species, with no malignancy identified.Our report highlights the diagnostic difficulties in the post-radiotherapy cancer patient presenting with symptoms suggestive of aggressive sino-nasal disease. Invasive fungal sinusitis closely mimics the clinical and radiological findings of several neoplastic processes. We discuss the clinical and radiological characteristics of pathologies that may mimic invasive fungal sinusitis. Histological examination remains the gold standard for diagnosis, and early fungal staining is crucial. Furthermore, one should not presume the initial histopathological diagnosis to be confirmatory of isolated fungal disease. Repeat radiological investigations for disease resolution and histopathologic re-evaluation if required should be performed, keeping in mind possibility of coexisting malignancy.

Impact of household income on survival in solid malignancies with synchronous brain metastases: A population-based study.

142 Background: Solid malignancies presenting with brain metastasis at the initial diagnosis usually carry a poor prognosis. Increased incidence of brain metastasis can be attributed to the advancements in neuroimaging techniques and improvements in the treatment of solid malignancies. The role of socioeconomic factors in cancer survival is being increasingly recognized. In this study, we analyzed the effect of median household income on survival outcomes in patients diagnosed with brain metastasis at the time of diagnosis of primary malignancies from 2010 to 2020. Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER) Program 17 registry (November 2022 submission) database for four primary sites of cancers based on their high propensity to develop brain metastases- Lung and/or Bronchus, Breast, Kidney and/or Renal Pelvis, and Melanoma. Patients with a median household income (MHHI) greater than 75,000 per year were classified as a high-income group, whereas those less than 75,000 per year were low-income. Patients diagnosed with malignancy during autopsy or via death certificate and with incomplete data were excluded. Kaplan-Meier method was used for 2-year survival rates and overall survival analyses. Cox regression analysis was used to calculate hazard ratios (HR). Results: A total of 66493 patients were identified across the four primary sites of tumors. Lung and/or bronchus tumors comprised most of the cases (n = 58,324). 25337 patients were in the high-income group, and 41156 patients comprised the low-income group. Median survival in the low-income group was 4 months, and in the high-income group was 5 months, with a 2-year survival rate of 11% and 18% respectively. Patients in the high-income group had better survival outcomes than the low-income [HR:0.88, 95% CI:0.86-0.90, p<0.001]. Additionally, the high-income group had 19% higher odds of receiving chemotherapy [OR:1.19, 95% CI:1.16-1.23, p<0.0001]. Amongst the cancer subgroups, household income did not have a significant effect on survival in patients with kidney and/or renal pelvis tumors [HR:0.97, 95% CI:0.88-1.06, p=0.5]. The 2-year survival rates are outlined (Table). Conclusions: Our analysis highlights a modest improvement in survival in the patient population with higher median household income. This difference could be attributed to the greater accessibility to treatment modalities and other resources for patients with higher household incomes. Further studies are needed to address socioeconomic disparities in survival for patients with solid malignancies having synchronous brain metastases. 2-year survival rates (95% CI). Cancer Groups Low-income High-income Combined Cancers 11% (11-12%) 18% (18-19%) Lung and/or Bronchus 10% (10-11%) 17% (17-18%) Breast 27% (25-29%) 34% (31-37%) Melanoma 19% (17-21%) 23% (20-25%) Kidney and/or Renal Pelvis 15% (13-17%) 18% (15-21%)

Incidental detection of non-melanoma neoplasms in sentinel lymph node biopsy for melanoma staging: A retrospective case series.

Patients with malignant melanoma have an increased risk of developing secondary hematologic malignancy, and patients with hematologic malignancies have an increased risk of developing melanoma. Rarely, sentinel lymph node biopsies (SLNBs) collected for melanoma staging might harbor lymphoma or even carcinoma, which may represent a second primary malignancy (SPM). Biopsied lymph node(s) might serve as the first site of recognition for a SPM. Yet, there has been little systematic investigation regarding the characteristics of incidental SPMs detected on SLNB for melanoma staging. A series of cases of lymphomas and carcinomas were detected incidentally during SLNB for melanoma staging from two tertiary academic centers between 2000 and 2021. Fifteen cases of incidentally detected SPMs were reviewed, comprising 12 lymphomas and three carcinomas. The most common incidentally detected second malignancy was chronic lymphocytic leukemia/small lymphocytic lymphoma (60%, 9/15). There were three cases of incidentally detected metastatic carcinoma. Of all incidentally detected malignancies, 2/3 carcinomas and 4/12 lymphomas represented first-time diagnoses of SPM in a melanoma patient. Forty percent of cases (6/15) also harbored metastatic melanoma in the sentinel lymph node. It is possible to incidentally detect SPMs in SLNBs for melanoma staging. Early detection of SPMs in melanoma patients has implications for the treatment of both incidental SPM and melanoma.

UTILITY OF CONTRAST-ENHANCED T2-FLAIR FOR IMAGING OF BRAIN METASTASESUSING A HALF-DOSE HIGH-RELAXIVITY CONTRAST AGENT IN COMPARISON WITH ROUTINE DOSE CONTRAST-ENHANCED BRAIN IMAGING

Aim & Objectives: This study aims to assess the efficacy of delayed contrast-enhanced T2 fluid-attenuated inversion recovery (CE-T2 FLAIR) by using half dose high relaxivity contrast agent to assess the degree of enhancement among the lesions and to detect additional metastatic brain lesions usually smaller lesions(<5mm), which are significantly missed on routine-dose CE-T1 weighted imaging (CE-T1WI). Material & Methods:The main source of data for this study was radiologically diagnosed lung cancer patients who were clinically suspected to have brain metastasis referred from various departments of Silchar Medical College and Hospital. The studywas carried out for a period of 1 year from March 1, 2023, to February 29, 2024, A total of 40 patients with brain metastases were scanned using a SIEMENS TIM AVANTO 1.5T scanner, routine MR pulse sequences pre- and post-contrast administration were acquired. Results: Out of 40 patients, males were more affected (57.5 %) than females (42.5 %). The highest number of cases were found between the 61-70 years age group with the lung (31 cases) being the most common primary malignancy causing brain metastases. A total of 90 lesions were detected among 40 patients which were grouped into A (25 lesions), B (36 lesions), and C (29 lesions) groups. A total of 6 lesions were missed on Routine dose contrast-enhanced brain imaging of which 2 lesions belong to group B (Rim enhancing lesions >5mm) and 4 lesions belong to group C (Lesions <5mm), however, these lesions were picked up on delayed half dose contrast-enhanced FLAIR images. The contrast ratio (CR) on 3 consecutive half dose CE-T2 FLAIR ranged between 59.09%-76.80%, suggesting that delay in imaging post-contrast administration resulted in a significant increase in the contrast ratio (CR) among metastatic lesions. Conclusions: CE-T1-weighted sequences and CE-T2 FLAIR sequences complement each other effectively in evaluating brain metastases. Bigger and homogenously enhancing lesions are best seen on CE-T1-weighted sequences. Smaller lesions and lesions showing rim enhancement are best visualized on delayed (5 min) CE-T2 fluid-attenuated inversion recovery (FLAIR) sequences with half the dose ofcontrast agent (gadobenatedimeglumine) compared to routine dose CE-T1-weighted sequences. This approach serves as a cost-saving measure for both patients and the healthcare system.

Is radiotherapy still the optimal initial choice for patients with early-stage low-grade follicular lymphoma in the modern era? A population-based study.

Despite radiotherapy (RT) is recognized as preferred initial therapy for early-stage low-grade follicular lymphoma (FL) by many international practice guidelines, the medical oncologist has improperly underutilized RT, and diverse management strategies, including systemic therapy (ST), combined modality (CM) and watch and wait (WW), are still used. Except survival outcomes, previous studies concerned little about the treatment-related toxicity, which is also important factor in choosing initial management strategy, especially second primary malignancies (SPMs). The aim of this study was to compare the overall survival (OS) and the SPMs risk between different management strategies, which can provide guidance for the choice of optimal initial management strategy. Data was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Finally, A total 10,900 patients were identified, in which 930 cases developed SPMs. The use of radiotherapy (RT) has remained consistently low, with a utilization rate of around 20%, while most patients have received watchful waiting (WW) and systemic therapy (ST). In the rituximab era, multivariate analysis indicated that RT exhibited significantly superior OS and did not increase SPMs risk in comparison with ST and WW. At the same time, although there were no significant differences in OS between CM and RT, RT had significantly lower SPMs risk in comparison with CM. The use of RT improved the OS and did not increase the SPMs risk in comparison with other management strategies. Considering the low application rate of RT, oncologists should emphasize and increase the use of RT as an initial management strategy in patients with early-stage low-grade FL.

Biallelic Mismatch Repair Deficiency in Children and Adolescents: A Review of Published and Unpublished Data from India—Need for an Indian Consortium

Abstract Introduction Biallelic mismatch repair deficiency or constitutional mismatch repair deficiency (CMMRD) is a rare and aggressive pediatric cancer predisposition syndrome that occurs as a result of homozygous (biallelic) pathogenic variants in mismatch repair genes. The primary malignancies that occur in CMMRD are mainly hematological and brain malignancies. Most published data are from the western populations and the Middle East. Data from India are limited to case reports. We performed an analysis to determine the prevalence of CMMRD in the Indian population. Materials and Methods All children aged less than 18 years with a diagnosis of CMMRD from various centers in India were included. CMMRD confirmed using genetic, molecular, and clinical criteria by an international consensus was included in the analysis. Literature search and data submitted by individual centers were reviewed. Results The analysis revealed that 22 children had genetically confirmed CMMRD. The median age of the cohort was 6.5 years, with a male predominance (male:female, 2:1). The classical phenotype of café-au-lait macules was observed in 72.7 % of subjects. The most common pathological variant was found in the PMS2 gene, which accounted for 77.3 % of children. Hematological malignancy (T cell acute lymphoblastic leukemia) was the most common primary malignancy in our study that occurred at a median age of 5 years (interquartile range 4–6 years) followed by brain tumors. The age at initial presentation for CMMRD with mutations in MSH2, MSH6, and PMS2 was 5.4, 4, and 7.5 years, respectively. Conclusion The diagnosis of CMMRD requires a high index of suspicion for the early diagnosis, management, surveillance, counseling, and testing of family members. The awareness about CMMRD in clinicians is important so that diagnosis is made early, and a second malignancy is detected and treated early. The need for an Indian consortium to determine the actual burden of the disease, genetic characteristics, and course of illness in our country has been emphasized.

Nanoparticle Delivery of an Oligonucleotide Payload in a Glioblastoma Multiforme Animal Model.

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain malignancy for which there is no cure. The blood-brain barrier is a significant hurdle in the delivery of therapies to GBM. Reported here is an image-guided, iron oxide-based therapeutic delivery nano platform capable of bypassing this physiological barrier by virtue of size and accumulating in the tumor region, delivering its payload. This 25 nm nano platform consists of crosslinked dextran-coated iron oxide nanoparticles labeled with Cy5.5 fluorescent dye and containing antisense oligonucleotide as a payload. The magnetic iron oxide core enables tracking of the nanoparticles through in vivo magnetic resonance imaging, while Cy5.5 dye allows tracking by optical imaging. This report details the monitoring of the accumulation of this nanoparticle platform (termed MN-anti-miR10b) in orthotopically implanted glioblastoma tumors following intravenous injection. In addition, it provides insight into the in vivo delivery of RNA oligonucleotides, a problem that has hampered the translation of RNA therapeutics into the clinic.

Is Information About Musculoskeletal Malignancies From Large Language Models or Web Resources at a Suitable Reading Level for Patients?

Patients and caregivers may experience immense distress when receiving the diagnosis of a primary musculoskeletal malignancy and subsequently turn to internet resources for more information. It is not clear whether these resources, including Google and ChatGPT, offer patients information that is readable, a measure of how easy text is to understand. Since many patients turn to Google and artificial intelligence resources for healthcare information, we thought it was important to ascertain whether the information they find is readable and easy to understand. The objective of this study was to compare readability of Google search results and ChatGPT answers to frequently asked questions and assess whether these sources meet NIH recommendations for readability. (1) What is the readability of ChatGPT-3.5 as a source of patient information for the three most common primary bone malignancies compared with top online resources from Google search? (2) Do ChatGPT-3.5 responses and online resources meet NIH readability guidelines for patient education materials? This was a cross-sectional analysis of the 12 most common online questions about osteosarcoma, chondrosarcoma, and Ewing sarcoma. To be consistent with other studies of similar design that utilized national society frequently asked questions lists, questions were selected from the American Cancer Society and categorized based on content, including diagnosis, treatment, and recovery and prognosis. Google was queried using all 36 questions, and top responses were recorded. Author types, such as hospital systems, national health organizations, or independent researchers, were recorded. ChatGPT-3.5 was provided each question in independent queries without further prompting. Responses were assessed with validated reading indices to determine readability by grade level. An independent t-test was performed with significance set at p < 0.05. Google (n = 36) and ChatGPT-3.5 (n = 36) answers were recorded, 12 for each of the three cancer types. Reading grade levels based on mean readability scores were 11.0 ± 2.9 and 16.1 ± 3.6, respectively. This corresponds to the eleventh grade reading level for Google and a fourth-year undergraduate student level for ChatGPT-3.5. Google answers were more readable across all individual indices, without differences in word count. No difference in readability was present across author type, question category, or cancer type. Of 72 total responses across both search modalities, none met NIH readability criteria at the sixth-grade level. Google material was presented at a high school reading level, whereas ChatGPT-3.5 was at an undergraduate reading level. The readability of both resources was inadequate based on NIH recommendations. Improving readability is crucial for better patient understanding during cancer treatment. Physicians should assess patients' needs, offer them tailored materials, and guide them to reliable resources to prevent reliance on online information that is hard to understand. Level III, prognostic study.

A rare expediting killer-primary thyroid gland sarcoma

Primary thyroid malignancies can be classified into differentiated type (follicular, papillary, medullary, and anaplastic) and un-differentiated type or non-epithelial malignancies, particularly lymphomas and sarcomas. The reported frequency of primary thyroid sarcoma (PTS) cases ranges from 0.01% to 1.5%. Based on this fact, we present a case report of rare primary thyroid sarcoma (PTS) in Hospital Sibu, Sarawak. Our patient is a 78-year-old lady with multiple co-morbidities and her clinical deterioration is so rapid that its progression mimics thyroid anaplastic carcinoma which is commonly seen in female elderly as well. To diagnose such uncommon thyroid malignancy, the histopathology of the tumour needs to be conducted with immunohistochemical staining. Radiographic imaging such as computed tomography or magnetic resonance imaging of whole body is required for staging purpose and to look for metastasis. We analyze the clinical presentations of PTS and discuss its treatment and prognosis. The treatment of PTS must be assessed individually on case-by-case basis as currently there is no general consensus on treating this cancer.

56Fe-ion Exposure Increases the Incidence of Lung and Brain Tumors at a Similar Rate in Male and Female Mice.

The main deterrent to long-term space travel is the risk of Radiation Exposure Induced Death (REID). The National Aeronautics and Space Administration (NASA) has adopted Permissible Exposure Levels (PELs) to limit the probability of REID to 3% for the risk of death due to radiation-induced carcinogenesis. The most significant contributor to current REID estimates for astronauts is the risk of lung cancer. Recently updated lung cancer estimates from Japan's atomic bomb survivors showed that the excess relative risk of lung cancer by age 70 is roughly fourfold higher in females compared to males. However, whether sex differences may impact the risk of lung cancer due to exposure to high charge and energy (HZE) radiation is not well studied. Thus, to evaluate the impact of sex differences on the risk of solid cancer development after HZE radiation exposure, we irradiated Rbfl/fl, Trp53fl/+ male and female mice infected with Adeno-Cre with various doses of 320 kVp X rays or 600 MeV/n 56Fe ions and monitored them for any radiation-induced malignancies. We conducted complete necropsy and histopathology of major organs on 183 male and 157 female mice after following them for 350 days postirradiation. We observed that lung adenomas/carcinomas and esthesioneuroblastomas (ENBs) were the most common primary malignancies in mice exposed to X rays and 56Fe ions, respectively. In addition, 1 Gy 56Fe-ion exposure compared to X-ray exposure led to a significantly early incidence of lung adenomas/carcinomas (P = 0.02) and ENBs (P < 0.0001) in mice. However, we did not find a significantly higher incidence of any solid malignancies in female mice as compared to male mice, regardless of radiation quality. Furthermore, gene expression analysis of ENBs suggested a distinct gene expression pattern with similar hallmark pathways altered, such as MYC targets and MTORC1 signaling, in ENBs induced by X rays and 56Fe ions. Thus, our data revealed that 56Fe-ion exposure significantly accelerated the development of lung adenomas/carcinomas and ENBs compared to X rays, but the rate of solid malignancies was similar between male and female mice, regardless of radiation quality.

Synchronous Head and Neck Squamous Cell Carcinoma and Hematologic Malignancies

Synchronous occurrence of solid tumors and hematological malignancy is a rare condition. There is no standard management or therapy for this complicated situation. The authors systematically reviewed articles searched using online databases. The patients are predominantly male, and the average age is similar to each malignancy. According to these studies, most patients are treated in order of aggressiveness. However, when a patient has multiple primary malignancies, all of which are aggressive, the treatment decision is challenging. Due to the limited number of cases, it is hard to have a firm conclusion about an optimal treatment policy. It appears that poor outcomes are mostly related to less adequate therapy. Because the condition is complicated in such cases and there is no standardized treatment, patients should be treated on an individual basis with treatments customized to a given patient’s particular circumstances. In addition, multidisciplinary communication and cooperation are crucial in the management of these patients. More in-depth research is still needed to reach a more conclusive treatment strategy and predictable outcomes.