The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies.

UNASSIGNED: Limited data is available about the feasibility of stereotactic body radiation therapy (SBRT) for treating more than five extra-cranial metastases, and almost no data for treating more than ten. The aim of this study was to investigate the feasibility of SBRT in this polymetatstatic setting.
UNASSIGNED: Consecutive metastatic melanoma patients with more than ten extra-cranial metastases and a maximum lesion diameter below 11 cm were selected from a single-center prospective registry for this in-silico planning study. For each patient, SBRT plans were generated to treat all metastases with a prescribed dose of 5x7Gy, and dose-limiting organs (OARs) were analyzed. A cell-kill based inverse planning approach was used to automatically determine the maximum deliverable dose to each lesion individually, while respecting all OARs constraints.
UNASSIGNED: A total of 23 polymetastatic patients with a medium of 17 metastases (range, 11-51) per patient were selected. SBRT plans with sufficient target coverage and respected OARs dose constraints were achieved in 16 out of 23 patients. In the remaining seven patients, the lungs V5Gy < 80 % and the liver D700 cm3 < 15Gy were most frequently the dose-limiting constraints. The cell-kill based planning approach allowed optimizing the dose administration depending on metastases total volume and location.
UNASSIGNED: This retrospective planning study shows the feasibility of definitive SBRT for 70% of polymetastatic patients with more than ten extra-cranial lesions and proposes the cell-killing planning approach as an approach to individualize treatment planning in polymetastatic patients\'.

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BACKGROUND: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis (\'late VTE\') is scarce, particularly in young survivors.
METHODS: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses.
RESULTS: Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer.
CONCLUSIONS: VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

(1) Background: Following the results of RAINBOW and REGARD trials, ramucirumab was approved as the standard second-line treatment for patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) cancer, alone or in combination with paclitaxel. The present study aimed to evaluate the efficacy and safety of ramucirumab in the Romanian population during every-day clinical practice. (2) Methods: A two-center, retrospective, observational study evaluated patients with metastatic gastric and GEJ cancer treated with ramucirumab monotherapy or associated with paclitaxel. The patients were treated between 2018 and 2022 in two Romanian centers as follows: 18 patients underwent treatment with ramucirumab monotherapy, while 51 received the combined treatment regimen. Study endpoints included median progression-free survival (PFS), median overall survival (OS), and the evaluation of treatment-induced adverse events (AEs). (3) Results: In the study cohort (n = 69), the most frequent treatment-induced AE in the ramucirumab plus paclitaxel arm was hematological toxicity; the most common AE for patients treated with ramucirumab monotherapy was fatigue and headache. Overall, the median PFS was 4.7 months (95% CI: 3.4-5.9 months) and median OS was 18.23 months (95% CI: 15.6-20.7 months). PFS was correlated with the number of treatment cycle administrations, Eastern Cooperative Oncology Group performance status at treatment initiation, and metastatic site (visceral vs. peritoneal). OS was correlated with the number of treatment cycles administered and human epidermal growth factor receptor-2 status. (4) Conclusions: The results support the previously described toxicity profile for ramucirumab monotherapy or associated with paclitaxel and demonstrated a relatively superior median PFS.

OBJECTIVE: Pathologic fractures of the extremities due to carcinoma metastases require individual and patient prognosis-related stabilization procedures. Quick remobilization of the patient to restore the quality of life is of high importance, especially in the case of subtrochanteric and diaphyseal femoral fractures. In our retrospective cohort study, we evaluated intraoperative blood loss, length of operation, complication rate, and regain of lower extremity function in plate compound osteosynthesis (PCO) versus intramedullary nailing (IM) for subtrochanteric and diaphyseal pathologic fractures of the femur.
METHODS: Between January 2010 and July 2021, we retrospectively reviewed 49 patients who were treated at our institution for pathologic fractures of the subtrochanteric and diaphyseal femurs for group differences in terms of blood loss, length of operation, implant survival, and Musculoskeletal Tumor Society (MSTS) score.
RESULTS: We included 49 stabilization procedures of the lower extremity due to pathologic fractures of the proximal or diaphyseal femur, with a mean follow-up of 17.7 months. IM (n = 29) had a significantly shorter operation time than PCO (n = 20) (112.4 ± 9.4 and 163.3 ± 15.96 min, respectively). We did not detect any significant differences in terms of blood loss, complication rate, implant survival, or MSTS score.
CONCLUSIONS: Based on our data, pathologic subtrochanteric and diaphyseal fractures of the femur can be stabilized with IM, which has a shorter operation time than PCO, but the complication rate, implant survival, and blood loss remain unaffected.

OBJECTIVE: The aim of the study was to evaluate the baseline data of women with breast cancer (BC) undergoing treatment in an intercontinental comparison.
METHODS: This study included 99,571 women with BC from Europe (70,834), Asia (18,208), and Latin America (10,529) enrolled between 2017 and 2021, based on data from IQVIA\'s Oncology Dynamics database. This source is supplied with information by means of a cross-sectional partially retrospective survey collecting anonymized data on inpatients and outpatients treated by a representative panel of oncologists. A multivariable logistic regression model was used to investigate the probability of metastases.
RESULTS: The data available in Asia (98%) and Latin America (100%) were hospital data, while in Europe, patients were treated both in hospitals and in office-based practices (62%, 38%). The mean age in Asia and Latin America (57 ± 13) was lower than in Europe (61 ± 13; p < 0.001). Lobular BC was diagnosed twice as often in Europe compared to Asia and Latin America (15.2%, 9.8%, 8.0%). The number of patients with metastasized hormone receptor-positive (HR +) BC was significantly higher in Europe and Latin America than in Asia (76%, 68%; p < 0.001). The highest number of women with metastasized BC was reported in Europe (26% compared to 14% and 20%, respectively, in Asia and Latin America). Across the continents, the percentage of women with BC who experienced metastases was 51-61% for bone, 30-39% for lung and 25-32% for liver, followed by 3-6% for skin and 3% for brain.
CONCLUSIONS: Women with BC treated in Europe tend to be significantly older and more likely to develop metastases than women in Asia and Latin America, except for lung metastases.

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome.

Having metastatic disease at diagnosis poses the great risk of death among AYAs with cancer from all sociodemographic subgroups. This “landscape” study utilized United States Surveillance, Epidemiology, and End Results Program data from 2000−2016 to identify subgroups of AYAs at highest risk for presenting with metastases across twelve cancer sites having a poor-prognosis (5-year survival <50% with metastases). Adjusted odds ratios for risk of metastatic disease presentation were compared for AYAs in aggregate and by sociodemographic subgroup (race/ethnicity, sex, socioeconomic status [SES]). In general, AYAs who were male, racial/ethnic minorities, or low SES were at consistently greatest risk of metastases. Strikingly, having metastatic melanoma was independently associated with multiple AYA sociodemographic subgroups, including males (aOR 3.11 [95% CI 2.64−3.66]), non-Hispanic Blacks (4.04 [2.32−7.04]), Asian Pacific Islanders (2.99 [1.75−5.12]), Hispanics (2.37 [1.85−3.04]), and low SES (2.30 [1.89−2.80]). Non-Hispanic Blacks were more likely to present with metastatic cancer in all sites, except for bone, rhabdomyosarcoma, and stomach. Low SES AYAs are more likely to present with metastatic melanoma, bone tumors, soft tissue sarcomas, breast, cervical, lung, and stomach carcinomas. Building on these results, future cancer-specific studies should investigate the connection between sociodemographic risk factors and biological drivers of metastases. This line of research has potential to inform targeted public health and screening efforts to facilitate risk reduction and earlier detection of these deadly diseases.

OBJECTIVE: Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB).
METHODS: In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38).
RESULTS: Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B.
CONCLUSIONS: The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation.