Incident learning is key to improving clinical quality and safety. This study evaluates the impact of workflow changes related to increasing remote work on incident learning in a radiation oncology clinic. We analyzed reported event data for three 12-month intervals: pre-COVID (March 1, 2019 - February 29, 2020), during-COVID (March 1, 2020 - February 28, 2021), and COVID-adapted (March 1, 2021 - February 28, 2022). Events were prospectively analyzed by our multi-disciplinary Quality and Safety Committee using an electronic incident learning system capture system. We evaluated event reporting rates, severity, associated/contributing factors, point of event origin and detection. Descriptive statistics and chi-square tests were used to compare characteristics between the three time intervals. Over the three years considered, 798 event reports were submitted and reviewed. The reporting rate (number of reported events per patient simulated) decreased over time: pre-COVID 0.18 [335/1834]; during-COVID 0.15 [245/1609]; and COVID-adapted 0.13 [218/1695]. The severity of events declined over time (p=<0.001). As time progressed, the location of event origin shifted towards earlier steps in our workflows (i.e. towards simulation-related imaging and treatment planning). Similarly, the point of event discovery shifted to earlier steps as well (ie. towards during pretreatment review and verification, and away from treatment delivery and management). Communication was frequently identified as a contributor during the latter two time periods while workload was less frequently cited compared to pre-COVID. The severity, site of origin/discovery of events and associated/contributing factors varied over time demonstrating shifts in the nature of events associated with changes in pandemic-induced workflows. Additional efforts to promote event reporting are needed to maintain the benefits of incident learning.
Mismatch repair-deficient (dMMR) endometrial cancer is highly sensitive to immune checkpoint inhibition. Although pembrolizumab combined with carboplatin and paclitaxel is now a first-line standard treatment for advanced or recurrent dMMR endometrial cancer, there is limited evidence regarding the effectiveness of this treatment for initially unresectable cancer. We report two patients with advanced dMMR endometrial cancer who achieved a pathological complete response (pCR) after initial systemic carboplatin-paclitaxel plus pembrolizumab therapy.Case 1 was a 77-year-old woman diagnosed with FIGO 2008 stage IIIB (cT3bN0M0) grade 3 endometrioid carcinoma who had suspected sigmoid colon and ureter involvement and poorly controlled diabetes mellitus. Primary surgery with complete resection was considered unfeasible because of the anticipated surgical invasiveness and high risk of postoperative complications; therefore, the initial treatment was systemic therapy with carboplatin-paclitaxel plus pembrolizumab. Marked radiologic regression was achieved, bowel resection was avoided at surgery, and a pCR was confirmed.Case 2 was a 60-year-old woman with FIGO 2008 stage IVB (cT1bN2M1) grade 1 endometrioid carcinoma with suspected metastases in the pelvic, para-aortic, and left supraclavicular lymph nodes. After six cycles of systemic carboplatin-paclitaxel plus pembrolizumab therapy, cytoreductive surgery showed no residual viable carcinoma, confirming a pCR. These cases demonstrate that chemo-immunotherapy can induce a pCR in advanced dMMR endometrial cancer and may deepen the treatment response. Initial carboplatin-paclitaxel plus pembrolizumab therapy may enable less invasive surgery. These findings support the investigation of less invasive approaches for dMMR endometrial cancer.
Multi-criteria optimization (MCO) is an advanced optimization technique that can be applied to any problem with multiple objectives that may be conflicting. MCO has been available in commercial treatment planning systems (TPS) for several years now and has been applied to treatment planning of many anatomical locations in a variety of ways. The MCO optimization method is based on the Pareto plans generation and is very powerful, but there are significant hurdles in terms of clinical implementation due to long computing times, lack of dosimetrists training and plan degradation after the optimized fluence is converted to deliverable. While some authors have studied the use of MCO in automation, no clinical implementation of an MCO-based auto-planning technique has been reported. This study aims to develop and clinically deploy an automated planning tool based on MCO for prostate and whole-pelvis radiotherapy. A Python script based on a commercial treatment planning system was developed to automate MCO, including Pareto plan generation, fluence plan selection, dose conversion, and post-processing. The tool underwent retrospective validation on 10 prostate patients with the input of four dosimetrists and a 10-month prospective pilot involving another three senior dosimetrists across different community sites. Dosimetrists evaluated plan quality and provided quantitative and qualitative feedback for iterative improvements of the tool. The study reports on the plan comparisons between the clinical and the MCO generated plans for retrospective patients. The study also reports the prospective use cases and the qualitative and quantitative evaluations from dosimetrists. Retrospective evaluations showed 82.5% of MCO prostate plans were clinically acceptable. The tool generated prostate plans in approximately 10.1 min and whole pelvis plans in 27.2 min. Dosimetric analysis revealed comparable plan quality to clinical plans, with MCO plans achieving lower organ-at-risk doses. In the pilot phase, the MCO tool was used for 41 prospective patients, producing plans that dosimetrists could refine to achieve clinical acceptability within a median of 10 min. This study demonstrates the successful development and clinical implementation of an MCO-based automated planning tool for generating acceptable VMAT plans for prostate and whole pelvis radiotherapy. The extensive pilot phase showcases an effective strategy for integrating automated planning solutions into routine clinical practice.
Both SMARCB1(INI-1)-deficient and FH (fumarate hydratase)-deficient renal cell carcinoma (RCC) have a male predominance, potentially overlapping high-grade histologic features, and typically poor clinical outcomes. SMARCB1(INI-1) deficiency is the characteristic pathogenic alteration in medullary (or medullary-like) RCC, which is aggressively treated with chemotherapy, primarily platinum-based. In contrast, a distinct set of agents, such as the combination of bevacizumab and erlotinib, is the principal systemic therapy consideration for FH-deficient RCC. SMARCB1 (INI-1) is a core subunit of the SWI/SNF complex, regulating chromatin remodeling and gene transcription through epigenetics. The accumulation of fumarate, resulting from the loss of FH, can alter DNA methylation and promote a CpG island methylator phenotype (CIMP), silencing tumor suppressor genes. Rare case reports of FH-deficient RCC with concurrent loss of SMARCB1 (INI-1) have been reported, which is likely due to secondary epigenetic silencing of SMARCB1. Herein, we report a unique RCC case with concurrent loss of SMARCB1 (INI-1) and FH expression by immunohistochemistry. Molecular studies demonstrated a SMARCB1 mutation, but no FH mutation was identified. Relatively low FH transcription was detected in the case, which raises the possibility of a pathogenic loss of SMARCB1 (INI-1), accompanied by a potential secondary, epigenetic loss of FH expression. Therefore, FH loss by IHC does not necessarily always indicate a pathogenic FH mutation. Further molecular studies are critical in determining the underlying pathogenic mutation.
As cancer survivorship rises, provision of information during cancer care is increasingly important, especially regarding potential impacts on patients' health-related quality of life. We sought to understand information needs patients had before initiating anti-cancer treatment using data from a qualitative study designed to examine appropriate recall periods in patient-reported outcome measures of physical function (PF). In this secondary analysis from the Patient Reports of Physical Functioning Study (PROPS) research program, we report on: What do patients wish they had known about their PF before starting treatment? In this secondary analysis, we examined transcripts from PROPS to describe what patients wish they had known about their PF before starting treatment. We used qualitative content analysis to analyze 72 semi-structured transcripts conducted with adults with cancer who had undergone anti-cancer treatment in the previous 6 months. The purpose of this analysis was to identify categories of patient information needs. Of the 72 participants, over half indicated a desire for additional information about their PF before starting treatment, including the impact of side effects/symptoms, such as pain and fatigue, on PF, or a better understanding of expectations for PF. Most of these participants reported PF limitations during the interview. The remaining participants reported feeling fully informed, with most reporting no PF limitations. Patients are interested in learning about the impact of treatment on their PF, but the amount of detail desired varies. Providing personalized information may enhance shared decision-making, empower patients in self-management and treatment decisions, and support timely referrals to specialists. These findings highlight the need for tailored communication strategies in cancer care to better address patient concerns and improve overall treatment experiences.
Pyridine chalcone derivatives are emerging anticancer candidates with potent activity against different types of cancer. However, their developmental and angiogenic safety profiles remain unexplored. In our lab, we recently generated a series of novel pyridine-based chalcone analogs; we reported that two of them, OH17 and OH25, are highly effective against different types of cancer cell models. We herein investigated the effects of these two compounds on early embryonic development and normal vascular formation using the chicken embryo and chorioallantoic membrane (CAM) models. In addition, qPCR analysis of key apoptosis- and angiogenesis-related markers was performed on organs collected from treated embryos, together with in vitro evaluation using normal embryonic fibroblast cells (NEFCs). Our data revealed that both OH17 and OH25 did not affect the normal development of the embryos and their survival rate when they were exposed to these two compounds at 3 days of incubation. Meanwhile, the CAM analysis showed no significant alterations in vessel area, branching, or density, with only a minor reduction in average vessel length. More significantly, gene expression patterns of apoptotic and angiogenic key markers remain unchanged across different tissues from several organs of exposed embryos. Consistently, NEFCs retained normal viability and fibroblast morphology following treatment with the two compounds. Together, these findings, combined with our previous reports, demonstrate OH17 and OH25 safety in addition to their potent anticancer activity. Thus, paving the way towards a favorable therapeutic window for these two compounds in support of their further development as promising anticancer agents.
Carbon-11 methionine positron emission tomography (11C-methionine PET; Met-PET) is widely used in neuro-oncology for preoperative tumor characterization, differentiating recurrence from radiation necrosis, and determining stereotactic biopsy targets. Although its role in gliomas has been well established, evidence supporting its value in germ cell tumors, particularly teratomas, remains limited. An 18-year-old man presented with diplopia, photophobia, and a headache. Magnetic resonance imaging (MRI) revealed a pineal tumor. Serum AFP was 31.5 pg/mL, serum β-HCG < 1.0 mIU/mL, and CSF PLAP 23.6 pg/mL. After three courses of CARE chemotherapy and local radiotherapy, gross total resection was performed at another hospital. He subsequently developed hydrocephalus and underwent endoscopic third ventriculostomy at our institution. MRI and Met-PET showed no residual lesions. Additional ICE chemotherapy resulted in the normalization of tumor markers. However, MRI performed 4 months after resection demonstrated a new enhancing lesion in the right posterior thalamus, and Met-PET revealed new uptake (SUVmax, 2.64; TNR, 2.08), suggesting recurrence. A second craniotomy achieved gross total resection of the whitish, elastic, well-demarcated lesion. Histopathology showed mainly granulomas with inflammatory changes, but no viable tumor cells. The postoperative course was uneventful, and no recurrence has been observed for 3 years. This case suggests that in germ cell tumors, particularly teratomas, Met-PET findings may be misleading and do not necessarily indicate viable tumor tissue. Further studies are required to clarify the clinical significance of Met-PET for teratomas.
The incidence of secondary retroperitoneal lymph node tuberculosis (TB) in patients with acute myeloid leukemia (AML) is relatively low, making it challenging to diagnose in clinical practice. This paper reports an AML patient who developed TB after chemotherapy, confirmed by positive T-SPOT results from the ultrasound-guided retroperitoneal lymph node biopsy. Eventually, the patient achieved negative conversion on T-SPOT test following individualized anti-TB treatment. This case highlights the necessity of the diagnosis of tuberculosis when infections occur in leukemia patients. Clinically, ultrasound-guided biopsy enables timely diagnosis, and favorable outcome can be attained by selecting an appropriate therapeutic regimen.
The optimal radiotherapy strategy for prostate cancer (PC) patients with high nodal risk remains debated. This prospective phase II study reports long‑term clinical outcomes, toxicity, and patient‑reported outcomes in men with PC treated with whole‑pelvis radiotherapy and dose escalation to MRI‑identified intraprostatic lesions and PET‑positive pelvic lymph nodes. Eighty‑five PC patients with high nodal risk or up to three pelvic nodal metastases were enrolled between 2013 and 2017. Radiotherapy delivered 77 Gy to the prostate and 56 Gy to pelvic nodes in 35 fractions, with escalation to 70 Gy for PET‑positive nodes and 84 Gy for MRI‑defined intraprostatic lesions when feasible. Endpoints included biochemical progression‑free survival, overall survival, toxicity, and longitudinal patient‑reported outcomes. Seventy-eight patients underwent radiotherapy. Of these, 42 received an intraprostatic boost and were classified as the per-protocol population. Median follow‑up was 7.8 years, and 26% had N1 disease. For the full cohort, five‑year biochemical progression‑free survival was 76%, with poorer results among patients with RECIST‑positive nodal involvement. Five‑year overall survival was 95%. Acute grade ≥ 2 genitourinary and gastrointestinal toxicities occurred in 33 and 23%, respectively, and decreased over time. No grade ≥ 3 gastrointestinal toxicity was observed. Patient‑reported outcomes showed low long‑term urinary and bowel bother. Whole‑pelvis radiotherapy with targeted dose escalation was well tolerated. The high proportion of patients not receiving an intraprostatic boost underscores methodological challenges and emphasises the need for standardised imaging interpretation and delineation guidelines.
Castleman disease (CD) is a rare lymphoproliferative disorder classified by anatomic site and clinical presentation. Pediatric CD is exceedingly uncommon, with only limited cases reported in the literature. This cohort study encompassed 30 pediatric patients (aged ≤ 18 years) diagnosed with CD. Statistical analyses and advanced modeling were conducted using SPSS version 25.0 and R version 4.3.2. Data collected included demographic information, histopathological findings, laboratory results, and imaging characteristics. Among 30 pediatric CD patients, 19 had unicentric CD (UCD) and 11 had multicentric CD (MCD). UCD patients (12 males, 7 females) had a median diagnosis age of 11 years (IQR, 7.25-13.75; range, 3-18), median diagnostic delay of 2.4 months (IQR, 1.1-8.5), and median follow-up of 16.5 months (IQR, 6.75-27); MCD patients (5 males, 6 females) had a median diagnosis age of 15 years (IQR, 12-16; range, 11-16); median diagnostic delay of 1.77 months (IQR, 0.63-4.17); and median follow-up of 9.5 months (IQR, 5.75-26.5). Compared with MCD, UCD patients had significantly higher MCV (85.04 ± 6.60 fL), ALC (2.67 ± 0.93 × 10⁹/L), Hb (130.03 ± 13.22 g/L), and serum albumin (45.12 ± 4.01 g/L), while MCD patients had higher diagnostic age, PLT (281.37 ± 67.06 × 10⁹/L), globulin (24.35 ± 3.54 g/L), and CRP. UCD had significantly lower incidences of multicentric involvement, hepatosplenomegaly, and systemic symptoms (p < 0.05). Histopathologically, hyaline-vascular subtype predominated in UCD, and mixed hyaline-vascular-plasma-cell subtype was more common in MCD (p = 0.004). Surgery was the primary treatment for UCD, while chemotherapy predominated for MCD (p < 0.001). Night sweats, dizziness, and headache did not affect diagnostic delay or maximum lesion cross-sectional area (p > 0.05). Firth's penalized univariate exact logistic regression showed MCV, Hb, PLT, and somatic symptoms approached statistical significance for outcomes; LASSO regression identified fatigue, MCV, and medical history as core prognostic predictors, while Ridge regression indicated positive signs, fatigue, and MCV as high-risk variables, with globulin, albumin, and complications exerting protective effects, and both models had good predictive efficacy.  Significant differences (p < 0.05) existed between single-center and multicenter CD cohorts in clinical and laboratory parameters. The single-center group had higher MCV, ALC, Hb, and albumin, and lower age, PLT, and globulin. It also had significantly lower rates of fever, hepatosplenomegaly, surgical biopsy, and systemic symptoms at initial diagnosis. Pathologically, hyaline vascular type predominated in the single-center group, while the multicenter group had mixed subtypes. The single-center group primarily underwent surgery, and the multicenter group favored chemotherapy. Subgroup analysis of symptoms showed no significant differences in delayed diagnosis time or maximum lesion cross-sectional area (p > 0.05). Firth's exact logistic regression and LASSO/Ridge penalized regression identified MCV, fatigue, and medical history as potential CD prognostic factors, with penalized models showing good predictive performance in this small-sample study. • Castleman's disease (CD) is a rare lymphoproliferative disease, which can be classified according to anatomical location and clinical manifestations. Children's CD is extremely rare and the literature reports are limited. It is mainly divided into unicentric (UCD) and multicentric (MCD). • The common pathological subtypes of CD are hyaline vascular type, plasma cell type and mixed type. UCD is mainly treated by surgery, and MCD is mainly treated by chemotherapy. Night sweats, dizziness, and headache do not affect the diagnostic delay and maximum cross-sectional area of children with CD. • Thirty children with CD were included in this study, and it was clear that there were significant differences between UCD and MCD in demography, laboratory indicators, clinical phenotype and pathological subtype, and UCD was more benign. • Through a variety of regression models, core prognostic predictors such as MCV, fatigue, and past medical history are screened out, and high-risk and protective factors are identified, and the model has good predictive efficacy in small samples.
With the development of new sequencing technologies, metagenomic next-generation sequencing (mNGS) has become a diagnostic tool for respiratory tract infections. Patients with cancer may develop pneumonia caused by infections or antitumor therapy. Therefore, pneumonia in patients with cancer is more complex than that in healthy individuals. Currently, few reports are available on the use of mNGS for diagnosing pneumonia in patients with cancer. In this retrospective study, 14 patients with cancer diagnosed with pneumonia in March 2023 were enrolled from the Emergency Department of the Chinese Academy of Medical Sciences Cancer Hospital. Sputum samples from the patients were examined using conventional tests and mNGS to identify pathogens. The mNGS and conventional test results were compared to assess the diagnostic yield in patients with cancer. The overall pathogen detection rate of mNGS was 64.29% (9/14), with corresponding diagnostic sensitivity, specificity, false-negative rate and false-positive rate of 90.00%, 25.00%, 10.00% and 75.00%, respectively. Among 13 paired sputum specimens, mNGS exhibited a numerically higher pathogen detection rate (61.54%, 8/13) than conventional diagnostic assays (38.46%, 5/13). McNemar's paired chi-square test demonstrated no statistically significant difference between the two detection methods (p = 0.37), and Kappa concordance analysis generated a coefficient of 0.27 (p = 0.23), suggesting poor inter-method consistency. Compared with conventional tests, mNGS detected additional pathogens in 8 specimens and identified a greater number of pathogens in 9/14 (64%) samples. Moreover, mNGS results led to diagnostic revisions and subsequent antimicrobial therapy adjustments in 64% (9/14) of enrolled patients. Additionally, mNGS detected antibiotic resistance genes in five patients, which provided guidance for antibiotic selection. Metagenomic next-generation sequencing (mNGS) showed potential value in pathogen detection, as it appeared to identify pathogens more rapidly and comprehensively than conventional methods. It may provide auxiliary support for the diagnosis and treatment of pneumonia in this vulnerable population.
To demonstrate our endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results and review in detail the recommendations of the American College of Chest Physicians (ACCP) guidelines and local clinical practice at a tertiary Thoracic Oncology center. Consecutive patients diagnosed with non-small cell lung cancer (NSCLC) between September 2008 and December 2017 who underwent EBUS-TBNA of mediastinal and hilar lymph nodes (LNs) for diagnosis and staging were enrolled. Systematic LN staging was performed. All patients were classified into 2 groups on the basis of the ACCP guidelines. Patients with clinical N0 (cN0) and peripheral NSCLC measuring 3 cm or less, for whom LN staging is not recommended, were classified into group A (n = 43). Patients with cN1-3, central, and/or NSCLC measuring more than 3 cm, for whom LN staging is recommended, were classified into group B (n = 626). In total, 669 patients were included. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of LN staging were 85.0%, 100%, 100%, 84.7%, and 91.8%, respectively. In total, 11% of group A patients had N2 disease and 4% had N3 disease; however, only 1 of these cases was detected using EBUS-TBNA. Occult N2 disease is common in patients diagnosed as cN0 with peripheral <3 cm NSCLC. Further studies are needed to evaluate patient and tumor characteristics associated with occult LN metastasis in this patient population. Nevertheless, careful consideration should be given to the potential presence of LN metastasis within group A.
The Personalized Induction Therapy-1 (PIT-1) trial is a multicenter, randomized, phase 2 selection design study in which patients with stage IIIA (N2) non-squamous non-small cell lung cancer received pemetrexed plus cisplatin with bevacizumab or concurrent thoracic radiotherapy, both followed by surgery. Herein, we report the 5-year survival outcomes. Eighty-two patients (42 in the bevacizumab arm and 40 in the radiotherapy arm) received induction therapy, and 75 patients (38 and 37, respectively) underwent surgery. Five-year overall survival and progression-free survival were compared between arms in the 82 eligible patients. In addition, overall survival, relapse-free survival, and patterns of postoperative relapse were analyzed in the 75 patients who underwent surgery. Among the 82 treated patients, the 5-year overall survival rate was 63.5% (95% CI, 46.9-76.1) in the bevacizumab arm and 57.2% (95% CI, 40.5-70.8) in the radiotherapy arm (P = .57). The 5-year progression-free survival rate was 26.2% (95% CI, 14.1-40.0) and 27.5% (95% CI, 14.9-41.7), respectively (P = .36). Recurrence of ipsilateral hilar or mediastinal lymph nodes (within the irradiation field) was significantly lower in the radiotherapy arm (n = 1, 3%) than in the bevacizumab arm (n = 7, 18%, P = .01). All patients with relapse in the PIT-1 trial (except 1 patient in the radiotherapy arm) received at least 1 subsequent therapy. Five-year survival outcomes did not differ between treatment arms. The radiotherapy arm exhibited sufficient local control within the irradiated field.
Uterine mesonephric-like adenocarcinoma (MLA) is a rare and biologically aggressive subtype of endometrial carcinoma, estrogen receptor (ER) and progesterone receptor (PR) are typically absent or exhibit very low expression in this type of cancer. The cornerstone of treatment is still surgical resection, frequently in combination with chemotherapy or radiation therapy. There is currently disagreement over the optimal therapeutic regimen. A 60-year-old postmenopausal woman presented with vaginal bleeding as the initial symptom. Computed tomography (CT) imaging revealed a uterine mass, and postoperative histopathology confirmed a diagnosis of mesonephric-like adenocarcinoma of the uterus. This case demonstrates dual ER/PR positivity, representing the first reported instance of this rare clinical subtype. This study aims to enhance clinicians' recognition and management of uterine mesonephric-like adenocarcinoma. MLA with hormone receptor expression may exhibit distinct biological behavior. Future studies with larger cohorts and longer follow-up are needed to explore whether these tumors could represent a candidate for endocrine-based therapeutic approaches.
Computed tomography pulmonary angiography (CTPA) is the gold standard for pulmonary embolism (PE) diagnosis, but patients with iodinated contrast allergies or renal insufficiency are often ineligible. CT-derived perfusion (CTP) is a novel, non-contrast method to quantify pulmonary perfusion from an inhale/exhale CT image pair (4DCT). The resulting CT-P information can be used to identify hypo-perfused regions associated with PE. This pilot study introduces a thresholding approach that estimates the number of lung lobes with perfusion deficits according to optimally selected CTP thresholds. The number of lobes indicated as low-functioning provides a score to categorize patients as PE-positive, negative, or inconclusive. We trained and validated the model on a retrospective dataset of 123 suspected PE patients, achieving 72% accuracy, 75% sensitivity, and 69% specificity, with 17% of cases inconclusive. To our knowledge, this is the first PE diagnostic model from non-contrast 4DCT, showing the feasibility of non-contrast PE diagnosis strategies.
Immune checkpoint inhibitors (ICIs) are critical in the modern treatment of advanced melanoma but can provoke immune-related adverse events (irAEs) with increased risk in patients having pre-existing autoimmune conditions. We present a case of Felty syndrome (FS) recurrence precipitated by a single dose of combination nivolumab plus relatlimab immunotherapy in a 71-year-old man with metastatic melanoma and a history of seropositive rheumatoid arthritis (RA) diagnosed several years earlier in the context of spontaneous FS. Following ICI, he presented with a neutrophil count of 0.0 cells/µL but without clinically active synovitis. He was promptly managed with intravenous methylprednisolone and methotrexate with rapid neutrophil recovery despite the ICI precipitant. In this report, we explore the differential diagnoses and treatment considerations, which highlight the importance of considering ICI-induced FS as a differential diagnosis in patients with a history of RA presenting with neutropenia. Early identification and collaborative care are vital for preventing life-threatening complications associated with neutropenia in this vulnerable patient population.
Lurbinectedin in combination with irinotecan showed synergistic antitumor activity in preclinical studies. A phase I/II trial (NCT02611024) evaluated this combination in patients with advanced solid tumors. The phase II stage evaluated the antitumor activity of the recommended dose (RD) (lurbinectedin 2.0 mg/m2 on Day (D)1 plus irinotecan 75 mg/m2 on D1 and D8 q3wk with primary granulocyte colony-stimulating factor prophylaxis) in five tumor-specific cohorts. This pooled analysis describes the safety profile of this combination from 233 patients with different advanced solid tumors treated at the RD. Adverse events (AEs) and laboratory abnormalities were graded using NCI-CTCAE v.4. The most frequent AEs (any grade) related to treatment were fatigue (71% of patients/25% of cycles), diarrhea (62%/17%), nausea (59%/18%), vomiting (35%/7%) and decreased appetite (32%/6%); the most common grade ≥ 3 AEs were fatigue (14%/2%), diarrhea (14%/2%) and febrile neutropenia (9%/1%). The most common grade ≥ 3 laboratory abnormality regardless of relationship was neutropenia (53%). The rate of discontinuation due to treatment-related AEs was 3% (n = 7 patients). There was one treatment-related death (0.4%) involving a 63-year-old male patient (0.4%) diagnosed with metastatic NEN who died due to grade 5 staphylococcal bacteremia. In conclusion, this pooled analysis shows a predictable and manageable safety profile for lurbinectedin in combination with irinotecan in patients with advanced solid tumors, with myelosuppression, fatigue and gastrointestinal disorders being the main toxicities observed.Trial code: ClinicalTrials.gov identifier: NCT02611024.
Radiotherapy has long been first-line treatment for brain metastases. However, CNS penetrating systemic therapies are increasingly used as first-line alternatives. There is little evidence guiding surveillance in this setting. Here we retrospectively assessed surveillance strategies at a single institution and associated outcomes. Records from 33 patients, evaluated from 2021-2024 and treated with systemic therapy alone for active brain metastases, were reviewed. Time from diagnosis to 1st, 2nd, and 3rd surveillance MRI, incidence of intracranial progression, survival, and neurological adverse events were assessed. Patients were stratified by whether treatment was supported by the 2021 ASCO-SNO-ASTRO guidelines. Treatment met guidelines for 14/33 patients. Median (range) time to 1st, 2nd, and 3rd MRI was 45 (18-207), 95 (46-204), and 180 (74-329) days, respectively. One-year cumulative incidence of local progression in the guideline group was 0.43 (95% CI [0.18-0.66]) and in the non-guideline group was 0.32 (95% CI [0.13-0.52], p=0.5). One-year cumulative incidence of brain radiation in the guideline group was 0.29 (95% CI [0.09-0.53]) and in the non-guideline group was 0.44 (95% CI [0.22-0.64], p=0.87). Two patients experienced safety events on systemic therapy (seizures). Use of CNS-penetrating systemic therapies to treat brain metastases outpaced national guidelines in this study. While surveillance imaging frequency was variable and recurrences were common, many patients were able to delay radiation for over one year, with infrequent safety events. As interest in and options for CNS-penetrating systemic therapy grow, evidence-based guidelines for surveillance will be warranted.
The term synchronous refers to 2 or more primary independent malignancies, when the second (or subsequent) arises within 6 months after diagnosis of the first malignancy. Synchronous endometrial and ovarian cancers are found in 10% of patients with ovarian cancer and 5% of patients with endometrial cancer. Using a variety of criteria, pathologists can distinguish synchronous primary tumors from metastatic disease. Primary surgical staging remains the gold standard for treating patients with synchronous endometrial and ovarian cancers. Adjuvant therapy is still controversial in the early stages of the disease. Genetic evaluation of patients with a positive family history may be crucial for quicker diagnosis and to identify those with familial cancer syndrome. We present the case of a 47-year-old premenopausal woman with abdominal pain who qualified for surgery due to suspicion of an ovarian tumor during a physical examination and imaging studies. After the final histopathologic examination, the patient was diagnosed with synchronous endometrial cancer, FIGO IA, and ovarian cancer, FIGO IIIC stage .
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoma with a poor prognosis. The human T-lymphotropic virus 1 (HTLV-1) is associated with immunodeficiency and increased extranodal involvement in patients with diffuse large B-cell lymphoma (DLBCL). We report on a 47-year-old woman with spastic paraparesis and hepatitis B who was diagnosed with the acute form of ATLL. The clinical picture reveals peripheral generalized lymphadenopathy and splenomegaly. Findings on a hematologic exam indicated leukocytosis with lymphocytosis. A bone marrow biopsy/aspiration confirmed 50% T-cell lymphoid infiltration. Biochemistry results revealed hypercalcemia and a high lactate dehydrogenase value. Results of a CT scan indicated abdominal and thoracic adenopathy as well as moderate splenomegaly. A supraclavicular lymph node biopsy established a DLBCL diagnosis. The final diagnosis was composite lymphoma, DLBCL, and ATLL. The CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], and prednisone) regimen was chosen due to the patient's ECOG performance status. Multiple infectious complications were diagnosed during chemotherapy-induced secondary aplasia. A complete remission, confirmed via PET-CT imaging, was obtained. After 1 month, a skin tumor on the upper right thigh was discovered and biopsied, and the histopathological exam and immunochemistry findings indicated Epstein-Barr virus-DLBCL lymphoma. The association of 2 aggressive lymphomas in a single HTLV-1 carrier is a rare report, and the evolution was severe, complicated by opportunistic infections, and unfavorable.