Number Of Metastases Research Articles

A comprehensive approach to defining the cutoff value of oligometastasis in head and neck squamous cell carcinoma.

Patients with limited distant metastatic disease, also known as oligometastasis, show better survival rates than polymetastatic patients, and may be amenable for curative-intent treatment. The definition of oligometastasis, however, is unknown, and no quantitative analyses on the cutoff value for oligometastasis have been performed before. This study aims to derive specific threshold values for the number of metastases and affected locations that defines oligometastatic disease in head and neck squamous cell carcinoma. A retrospective cohort study was conducted including all patients diagnosed with distant metastases between 2006 and 2021. For each patient, the number of distant metastases and affected locations was recorded on the basis of the available imaging at the time of diagnosis. Cox regression analyses and a machine-learning k-means algorithm were used to determine threshold values. A total of 384 patients untreated for their metastatic foci were analyzed. Most patients (n=207; 53.9%) had metastasis to one anatomic location, followed by metastases in two anatomic locations (n=62; 16.1%). The majority of patients had ≥9 metastatic foci (n=174; 45.3%), followed by one focus (n=74; 19.3%) and two foci (n=32; 8.3%). Cox regression and machine-learning k-means models showed that although the number of metastases did not predict survival, the number of affected locations did significantly (p<.001), by identifying a threshold of two locations. Contrary to the prevalent dogma, the definition of oligometastasis should not be defined by the number of metastases but rather by the number of affected locations, with a maximum number of affected locations set at two.

Different approach to M descriptor for future staging of oligometastatic disease in SCLC: A cross-sectional survival analysis.

This study aimed to investigate the impact of oligometastasis and the M descriptor on survival insmall cell lung cancer (SCLC). This multicenter, retrospectivestudy included patients with newly diagnosed extensive-stage SCLC(ES-SCLC) from 2010 to 2020. Subgroups: Group 1: single metastasis in a single organ, Group 2: 2-5 metastases in a single organ, Group 3: 6 or more metastases in a single organ, and Group 4: metastases in two or more organs. This classification was based on the 9th Staging-M descriptor. Three-year progression-free survival (PFS) and overall survival (OS) analyses were conducted. The mean age of the 439 patients was 62 ± 10years, and 89.5% of them were male. The mean PFS for Groups 1, 2, 3,4 was 10.7months (95% CI 8.9-12.5), 7.5months (95% CI 5.6-9.4), 4.3months (95% CI 2.9-5.7), and 5.4months (95% CI 4.7-6.1), respectively. PFS in Group 2 was significantly higher. The mean OS for Groups 1, 2, 3,4 was 13.3months (95% CI 11.2-15.3), 9.5months (95% CI 7.1-11.9), 7.1months (95% CI 4.5-9.7), and 6.9months (95% CI 6.0-7.9), respectively.OS in Group 1 was significantly higher. OS and PFS in the M1b group were significantly higher than in the M1c1 and M1c2 groups (p < 0.05) with no statistical difference between the M1c1 and M1c2 groups. There is no significant difference in survival between the M1c1 and M1c2 groups.In ES-SCLC, the number of metastases may be a more predictive factor for prognosis than the number of metastatic organs.

Well calculated is better than quickly calculated: Comparison of Pencil beam and Monte Carlo algorithms according to the number of lesions and fractionation in radiosurgery of multiple brain metastases

PurposeIn this work we compared pencil beam (PB) and Monte Carlo (MC) algorithms in single isocenter plans of multiple brain metastases radiosurgery (SIMM-SRS) plans using the quality indices reported for SRS. MethodThe plans were evaluated concerning the prescribed dose, fractions and the number of metastases. The quality indices studied were mean dose (Dmean), D95, Paddick conformity index (PCI), Radiation Therapy Oncology Group (RTOG) homogeneity (HIRTOG) and quality of coverage indices (QRTOG), gradient index (GI), efficiency index for targets (Gη12Gy) and organs at risk (OARη12Gy) and V12-V18 for brain. ResultsThe D95 for plans calculated with PB algorithm increased and differences were statistically significant (p < 0.001). For Dmean no differences were observed (p > 0.194). The PCI for the single-fraction cases showed statistical significant differences (p < 0.039). The PCI for the three-fraction cases did not show statistical significant difference (p < 0.569). However, the mean value of the index for all cases did not differ significantly between PB (0.84) and MC (0.81). The GI showed statistically significant differences, only for the plans with more than 10 metastases for a single-fraction (p = 0.0001). The Gη12Gy values reported are within the interval of 0.26–0.80, and for all cases, there were no statistically significant differences. ConclusionConsidering that MC is more accurate for small volumes and heterogeneities, and computational time is reasonable for clinical use, it should be selected in all cases for SIMM-SRS plans. We introduced the potential of novel indices as Gη12Gy, and OARη12Gy for clinical evaluation that potentially serve as optimization factor.

A randomized phase III trial of stereotactic ablative radiotherapy for patients with up to 10 oligometastases and a synchronous primary tumor (SABR-SYNC): study protocol

BackgroundEmerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor.MethodsOne hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes.DiscussionSABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making.Trial registrationClinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).

The Role of Repeated Surgical Resections for Recurrent Brain Metastases in Older Population.

Background and Objectives: The impact of surgery for recurrent brain metastases in elderly patients has been the object of debate due to limited information in the literature. We analyzed clinical outcome and survival of elderly patients with recurrent brain metastases in order to assess potentially beneficial role of surgery. Materials and methods: In total, 219 patients with recurrent brain metastases between 2007 and 2022 were identified, of which 95 underwent re-resection; 83 patients aged 65 and older were analyzed. A survival analysis was performed, and clinical outcomes were evaluated. Results: The median survival time after surgery for recurrent brain metastases was 6 months (95CI 4-10) in older patients and 8 (95CI 7-9) in younger patients (p = 0.619). Out of all the older patients, 33 who underwent surgical resection showed prolonged survival compared with patients who did not receive surgical resection (median: 14, 95CI 8-19 vs. 4, 95CI 4-7, p = 0.011). All patients had preoperative Karnofsky performance scores of >70, which did not deteriorate after surgery (87.02 ± 5.76 vs. 85 ± 6.85; p = 0.055). In the univariate analysis, complete cytoreduction was a favorable prognostic factor. The tumor volume, the number of metastases, extracranial disease progression, adjuvant radiation, and systemic therapy did not affect survival in this cohort. Conclusions: Patients aged 65 and older benefit from neurosurgical resections of recurrent brain metastases. Survival did not differ from that in younger patients, which can be explained by a better preoperative functional status. Moreover, independent of the extent of resection, older patients who underwent surgery showed better survival than patients who did not receive surgical treatment. Complete cytoreduction was a favorable prognostic marker.

Prognostic Significance of Baseline Clinical and [68Ga]Ga-PSMA PET Derived Parameters on Biochemical Response, Overall Survival, and PSA Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Undergoing [177Lu]Lu-PSMA Therapy.

In this study, we sought to identify the clinical baseline characteristics and pre-therapy 68Ga-PSMA PET derived parameters that can have impact on PSA (biochemical) response, OS and PSA PFS in patients with metastatic castration-resistant prostate cancer (mCRPC) who undergo RLT with [177Lu]Lu-PSMA-617. Various pre-treatment clinical and PSMA PET derived parameters were gathered and computed. We used PSA response as the criteria for more than a 50% decrease in PSA level, and OS and PSA PFS as endpoints. We assessed the collected parameters in relation to PSA response. Additionally, we employed univariable Cox regression and Kaplan-Meier analysis with log rank to evaluate the influence of the parameters on OS and PFS. A total of 125 mCRPC patients were included in this study. The median age was 68 years (range: 49-89). Among the cases, 77 patients (62%) showed PSARS, while 48 patients (38%) did not show PSA response. The median OS was 14 months (range: 1-60), and the median PSA-PFS was 10 months (range: 1-56). Age, prior history of chemotherapy, and SUVmax had a significant impact on PSA response (p<0.05). PSA response, RBC count, hemoglobin, hematocrit, neutrophil to lymphocyte ratio (NLR), alkaline phosphatase (ALP), number of metastases, wbPSMA-TV, and wbTL-PSMA significantly affected OS. GS, platelet count, NLR, and number of metastases were found to have a significant impact on PSA PFS. We have identified several baseline clinical and PSMA PET derived parameters that can serve as prognostic factors for predicting PSA response, OS, and PSA PFS after RLT. Based on the findings, we believe that these clinical baseline characteristics can assist nuclear medicine specialists in identifying RLT responders who have long-term survival and PFS.

402. BRAIN METASTASES FROM ESOPHAGEAL CANCER AFTER MULTIMODAL TREATMENT: EARLY DETECTION AND AGGRESSIVE LOCAL TREATMENT CAN LEAD TO BETTER OUTCOMES

Abstract Background International guidelines do not recommend imaging investigations to rule out the presence of BM (brain metastases) during clinical staging or follow-up in patients with oesophageal cancer. Patients with single or up to three BM can be considered oligometastatic: in our study we analysed patients with BM focusing on the management and outcomes of BM. Methods We retrospectively identified patients who underwent surgical resection for oesophageal adenocarcinoma or squamous cell carcinoma from 2006 to 2022 in our Upper GI division and subsequently developed brain metastasis (BM). Starting from January 2018, a brain CT scan was added to the routine follow-up procedures in our centre. We divided patients in two groups based on the treatment received for BM: local therapy group treated with surgery and/or stereotactic body radiation therapy/stereotactic radiosurgery (SBRT/SRS) versus no local therapy group treated with chemotherapy or whole brain radiotherapy (WBRT). Results 34 patients developed BM (three didn’t receive treatment); 23 patients in local therapy versus 8 in no local therapy group. Median overall survival (OS, from BM diagnosis to patient’s death or last follow-up) in local therapy group was 14.52 months whereas in no-local therapy 3.41 months, p&amp;lt;0.001. At univariable analysis predictors of OS were pathological stage, pathological response, GI-GPA score, number of metastases, treatment. In multivariable analysis, only pathological stage was statistically significative. We diagnosed 17 BM recurrence before 2018 (17 patients of 355, 4,7%) and 17 after 2018 with introduction of routine brain CT (17 of 217, 7.8%). Conclusion BM from oesophageal cancer benefit from local aggressive treatment in terms of overall survival and to apply a local treatment is necessary that BM are diagnosed early. The introduction of brain CT scan during follow up may have improved the detection rate of BM and therefore in our opinion routine brain CT scan could be necessary.

A novel prognostic score (HAMP) for head and neck cancer patients with single and multiple SBRT-treated lung metastases derived from retrospective analyses of survival outcome.

We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC). In this retrospective study, we examined selected factors associated with progression-free survival (PFS) and overall survival (OS) among 59 patients with HNC treated with SBRT for a total of 118 PMs, between 2009 and 2023. Factors related to survival were included in the prognostic scoring system. Prognostic factors including histology, age, number of metastases, and performance status at first SBRT were weighted differently depending on the strength of correlation to PFS and OS. Total prognostic scores (HAMP) ranged from 13 to 24 points, with a cut-off total score of ≤18 scoring points for patients in a high-risk (HR) subcohort, and of ≥19 scoring points for patients in a low-risk group (LR). Median PFS (23.8 vs. 5.5 months, p < 0.001) and OS (61.3 vs. 16.4 months, p < 0.001) were significantly longer in the low-risk group compared to the high-risk group. The HAMP score might be a convenient tool to facilitate individualized treatment decisions and appropriate follow-up. The accuracy and reliability of the score requires further evaluation in prospective studies.

The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma

IntroductionThe International Association for the Study of Lung Cancer developed a global multicenter database to propose evidence-based revisions for the ninth edition of the TNM classification of pleural mesothelioma (PM). This study analyzes the M category to validate eighth edition M category recommendations. MethodsCases were submitted electronically or by transfer of existing institutional databases for patients with histologically or cytologically confirmed PM. The presence and number of metastases (single versus multiple) in each of eight organ systems were reported for patients with M1 disease at diagnosis. Overall survival (OS) was calculated by the Kaplan-Meier method. Differences in OS were assessed by log-rank test. ResultsOf 7338 submitted cases, 3598 were eligible and 3221 had sufficient data for clinical staging; 228 cases (7%) were M1. Median overall estimated survival was inferior for M1 compared with M0 patients: 10.5 months versus 21.5 months, respectively (p < 0.0001); estimated 1-year survival was 46% versus 71%, respectively. OS differences between M categories were preserved within histologic subgroups. Among 158 patients with organ-specific documentation of M1 disease, there was no statistically significant difference in OS between those with intrathoracic versus more distant metastatic disease (14.4 mo versus 10.9 mo, p = 0.64). No significant survival difference was detected between patients with metastatic disease in a single-organ system versus multiple-organ systems (12.6 mo versus 8.8 mo, p = 0.45). ConclusionsThis evidence-based analysis of the M category for PM conforms with the eighth edition M descriptors. No changes are proposed in the ninth edition of the mesothelioma M category.

PSMA PET/CT SUVmax as a prognostic biomarker in patients with metachronous metastatic hormone-sensitive prostate cancer (mHSPC).

Metastatic hormone-sensitive prostate cancer (mHSPC) is treatment-resistant and generally considered incurable. The development of prostate-specific membrane antigen positron emission-computed tomography (PSMA PET/CT) has generated immense expectations due to its diagnostic accuracy in prostate cancer (PCa). PSMA expression of the primary tumor, quantified by SUVmax, is a predictor of oncological outcomes. The role of PSMA-PET/CT SUVmax in metachronous mHSPC treated with ADT plus second-generation antiandrogens (ARSI) is unknown. The main aim of this study was to evaluate 68Ga-PSMA-11expression (SUVmax) as a potential prognostic biomarker in patients with metachronous mHSPC treated with ADT and first or second-generation antiandrogens. A second aim was to determine the association between PSMA SUVmax and PSA response to hormone therapy. Patients diagnosed with metachronous mHSPC between July 2017 and February 2023 who developed biochemical recurrence following radical surgery (with or without salvage radiotherapy and/or ADT) or external radiation therapy (with or without ADT) were included. All patients underwent 68Ga-PSMA-11 PET/CT imaging and the SUVmax value was determined for all measurable locations. The SUVmax value was used for the semiquantitative analysis. The Wilcoxon method was used to compare responders (PSA reduction ≥ 50%) to non-responders (PSA reduction < 50%). The SUVmax value and hormone therapy were evaluated as independent variables relative to the PSA response rate or PSA reduction using the linear regression method. A mixed-effects model (ANOVA) was used for the comparisons. A total of 82 patients were included. Median follow-up was 11.7 months. On the linear regression analysis, patients with a high SUVmax treated with ADT + ARSI showed a greater PSA response (p = 0.034) than those treated with ADT + first-generation antiandrogens. In the mixed-effects model, SUVmax was significant (p = 0.041). On the univariate analysis, PSA at recurrence (HR, 3.2; 95% CI: 1.07-13.6; p = 0.078) and the number of metastases (HR, 4.77; 95% CI 1.1-26.1: p = 0.002) were associated with the type of hormone therapy administered. PSMA-PET/CT SUVmax is a prognostic biomarker that can be used to predict a PSA response to ADT + ARSI in patients with metachronous mHSPC. However, these findings need to be confirmed in larger prospective studies.

Oncological and functional outcomes of pathological fractures of lower extremities in patients with malignant bone tumors.

As managing pathological fractures of the extremities can be difficult, the present study aimed to present a treatment algorithm for lower extremity bone malignancies. A total of 38 patients with impending and pathological fractures were treated at the Department of Orthopedic Surgery in Kindai University Hospital. Age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcomes, follow-up period and the MSTS scores and ECOG-PS were compared in cases of primary malignant tumors and those cases of metastatic malignant tumors were retrospectively surveyed. Post-treatment MSTS scores in cases of impending and pathological fractures were compared between intramedullary nail fixation and non-intramedullary nail fixation procedures. Disease sites included the sub-trochanteric femur in 10 patients, trochanteric femur in 8, femoral diaphysis in 7, femoral neck in 5, bilateral trochanteric femur in 3, proximal tibia in 3 and distal femur in 2 patients. A total of 10 patients had metastases between 3-20 sites. The median pre-fracture ECOG-PS score was 1. Adjuvant radiotherapy was administered to 5, chemotherapy to 8 and radiotherapy with chemotherapy to 10 patients. Surgical procedures included intramedullary nails in 18 patients, tumor arthroplasty in 4, plate fixation in 3, artificial head replacement in three, compression hip screw (CHS) in 3, conservative treatment in 2, bilateral intramedullary nail fixation in 2 and artificial bone stem with combined intramedullary nail and plate fixation, right-sided artificial head replacement and left-sided CHS in 1 patient each. The MSTS score was 19.9±8.95 for intramedullary nail fixation and 24.3±7.45 for other procedures, with a negative association between the MSTS score and pre-fracture ECOG-PS. The median follow-up period was 8 months. The outcomes were as follows: Alive with disease, 23 patients; continued disease-free, 1 patient; and dead due to disease, 14 patients. The 1-year postoperative overall survival rate was 60.5%. Moreover, the group with metastatic malignant tumors, which had significantly worse ECOG-PS, had significantly lower MSTS scores than the group with primary malignant tumors. The authors' treatment algorithm for malignant bone tumors of the lower extremity was shown to be useful.

The varied clonal trajectory of liver and lung metastases of colorectal cancer

BackgroundThe liver and lungs are the most common sites of colorectal cancer (CRC) metastases. Their involvement can take five different clinical scenarios: lung metastases only, liver metastases only, lung metastases before liver metastases, liver metastases before lung metastases and simultaneous lung and liver metastases. Using clinical and morphological data we studied the clonal trajectory of these scenarios. Materials and methodsA total of 465 (CRC) patients with 7952 liver and 6406 lung metastases were evaluated. Metastases clinical route was deciphered from metastases number, timing, and linear/parallel ratio (LPR)- a computerized parameter used for deducing clonal trajectories. LPR of +1 suggest pure linear dissemination and −1 pure parallel. ResultsLung-only metastases: high percentage of metachronous disease with a long lead time and a low LPR suggest parallel dissemination. Liver-only metastases: Rare metachronous disease with a short lead time, and a high LPR suggest linear spread. Lung-before-liver metastases: rare solitary metastasis, a median gap of 21 months between the organs, high lung and low liver LPRs suggest linear progression to the lungs and parallel dissemination to the liver. Liver-before-lung metastases: low liver and high lung LPRs and a median gap of 16.5 months between the organs suggest parallel dissemination to the liver and linear spread from the liver to the lungs. Simultaneous liver and lung metastases: rare solitary metastasis and similar and high LPRs suggest simultaneous linear progression to both organs. ConclusionsCRC metastases have different dissemination trajectories in different clinical scenarios. This information can potentially impact on clinical management.

Anticancer Effects of Spiperone in C57BL/6 Mice with Emphysema and Lung Carcinoma.

The antitumor and antimetastatic activity of dopamine D2 receptor antagonists spiperone was studied in C57BL/6 mice in a model of combined pathology (emphysema and lung cancer). Emphysema was induced by administration of LPS and cigarette smoke extract. Lung cancer was induced by injection of Lewis lung carcinoma cells into the lung. It has been shown that under conditions of combined lung pathology, spiperone prevents inflammatory infiltration and emphysematous expansion of the lungs and reduces the size of the primary tumor node, the number of metastases, and the area of the lungs affected by metastases. Spiperone reduces the number of cancer stem cells (CSCs) in the lungs and blood of mice with combined pathology. CSCs isolated from the lungs and blood of mice with combined pathology treated with spiperone had a significantly lower potential to form a tumorosphere in vitro than CSCs from untreated mice with emphysema and lung carcinoma. Thus, blockade of dopamine D2 receptors is a promising approach for correcting combined lung pathology and can be used in the development of a method for treating lung cancer in patients with emphysema.

The role of intraoperative central lymph node biopsy in the treatment of clinically low-risk PTMC.

To evaluate the role of intraoperative frozen biopsy of central lymph nodes in central neck dissection and thyroidectomy in patients of unilateral, clinically negative nodes (cN0) papillary thyroid microcarcinoma (PTMC) without extra-glandular invasion. The clinical data of 465 patients were collected retrospectively. Part of prelaryngeal, pretracheal and ipsilateral paratracheal lymph nodes were taken for frozen pathological examination during the operation. Then the thyroid lobe on the tumor side and isthmus were excised, and central neck dissection of the affected side was performed in all patients. The number of metastases in entire central lymph nodes of the affected side can be obtained by postoperative paraffin pathology. If the number of positive lymph nodes during surgery is ≥3, contralateral gland resection was performed. In this group of 465 patients, there were 186 cases with central lymph node metastasis. The Kappa coefficient of consistency between frozen pathology and paraffin pathology in central lymph nodes was 0.605. The ROC curve for the number of intraoperative frozen metastases-postoperative pathological metastases over 5 showed that the AUC of the curve was 0.793, while the maximum Youden index was 0.5259, whose corresponding number of positive lymph nodes was 3. Intraoperative central lymph nodes biopsy can be used as an important indicator for the status of central lymph node metastasis in unilateral cN0 PTMC patients without extra-glandular invasion and a determinant for central lymph node dissection. While the number of positive lymph nodes intraoperatively is ≥3, total thyroidectomy should be considered.

Does 5-ALA Fluorescence Microscopy Improve Complete Resectability in Cerebral/Cerebellar Metastatic Surgery? A Retrospective Data Analysis from a Cranial Center.

(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases.

Treatment algorithm for metastatic malignancies in the lower extremities.

A high prevalence of proximal femoral metastases persists in patients with cancer, particularly regarding lower extremity fractures. This study offers a detailed analysis of clinical characteristics of patients undergoing surgical treatment for pathological or impending fractures, enhancing treatment strategies for metastatic malignancies. A total of thirty patients who underwent treatment of impending and pathological fractures at Kindai University Hospital (Osakasayama, Japan) were included. The retrospective study comprised parameters including age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcome and follow-up period. Post-treatment MSTS scores were compared in cases of impending and pathological fractures, and between intramedullary nailing and other surgical procedures. In addition, one-year postoperative survival rates were calculated. Furthermore, operative time, blood loss and survival rates were compared between impending and pathological fractures. The participants' median age was 70.5 years, with disease sites primarily in the subtrochanteric femur, trochanteric femur, femoral diaphysis, femoral neck and other locations. Pathologies included multiple myeloma and unknown primary, lung, breast, kidney, liver, gastric, esophageal and uterine cancers. The median ECOG-PS score pre-fracture was 2. Treatment approaches involved radiotherapy, chemotherapy and a combination of both. Surgical interventions included intramedullary nailing (16 cases), endoprosthesis (1 case), bipolar head replacement (3 cases) and compression hip screw (3 cases), among others. A negative correlation (R=-0.63) existed between MSTS and pre-fracture ECOG-PS scores. The operative time was significantly shorter in impending than in pathological fractures, with impending fractures showing significantly lower blood loss. The treatment algorithm for malignant bone tumors of the lower extremity provided in the present study was efficient, potentially optimizing treatment strategies for such cases, and contributing to improved patient care and outcomes in oncology and orthopedic surgery.

Phase II study of multidisciplinary therapy combined with pembrolizumab for patients with synchronous oligometastatic non-small cell lung cancer TRAP-OLIGO study (WJOG11118L): Feasibility analysis of induction therapy and local ablative therapy.

8564 Background: Several clinical trials have shown that local ablative therapy (LAT) to all sites of the disease might provide survival benefit for patients with oligometastatic non-small cell lung cancer (NSCLC). Few studies have evaluated feasibility of multiciliary therapy combined immune-checkpoint inhibitor plus chemotherapy with LAT to all sites of disease. Methods: This multicenter, single-arm, phase II trial enrolled untreated patients with stage IV NSCLC who had 3 or fewer metastatic lesions. All patients had received 2–4 cycles of a systemic treatment including pembrolizumab and platinum-doublet chemotherapy as induction therapy. LAT was administered to all residual lesions after induction therapy, followed by maintenance therapy including pembrolizumab. The primary endpoint is the progression-free survival (PFS) rate of 24 months from the date of initiation of LAT. The secondary endpoints are safety, response rate of induction therapy, PFS, overall survival, and proportion of implementation. The present analysis showed feasibility of induction therapy and LAT. Results: Between October 30, 2020, and August 12, 2022, 30 patients were enrolled. The number of metastases at diagnosis was one in 7 patients (7/30, 23%), two in 14 patients (14/30, 47%), and three in 9 patients (9/30, 30%). All patients received induction therapy, and the objective response rate was 21/30, 70% (95% confidence interval, 50% to 85%). Adverse events of grade 3/4 occurred in 21/30, 70%, including neutropenia (5/30, 17%), anemia (2/30, 7%), and thrombocytopenia (2/30, 7%). Seven patients did not receive planned LAT for the following reasons: disease progression (N=3), adverse events (N=2; pneumonitis grade 2, and hepatitis grade 3), sudden death (N=1), and one patient had proven stage III after induction therapy. Twenty-three patients (23/30, 77%) received planned LAT to all sites of residual disease. As LAT, five patients received surgery only, 12 patients received radiotherapy only, and 6 patients received both surgery and radiotherapy. Eighteen patients completed planned radiotherapy for 32 lesions (primary sites 22%, lymph node 25%, bone 25%, pulmonary metastasis 19%, brain 6% and adrenal 3%). Eleven patients received surgery (primary sites and lymph node) as LAT. Grade 3/4 adverse events during LAT occurred in 3 patients (3/23, 13%): rash (n=1), hypoxia (n=1) and CPK increased (n=1). There were no treatment-related deaths. Conclusions: Results of the TRAP-OLIGO study showed that multimodality treatment with platinum-based chemotherapy plus pembrolizumab and LAT had favorable implementation, and planned LAT was feasible in this population. Clinical trial information: jRCTs041200046 .

Antitumor Effects of an Anthocyanin-Rich Grain Diet in a Mouse Model of Lewis Lung Carcinoma.

Functional foods enriched with plant polyphenol anthocyanins attract particular attention due to their health-promoting properties, including antitumor activity. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Lewis lung carcinoma. Mice of the C57BL/6 strain were fed with wheat of near-isogenic lines differing in the anthocyanin content for four months prior to tumor transplantation. Although a significant decrease in the size of the tumor and the number of metastases in the lungs was revealed in the groups with both types of grain diet, the highest percentage of animals without metastases and with attenuated cell proliferation in the primary tumor were observed in the mice with the anthocyanin-rich diet. Both grain diets reduced the body weight gain and spleen weight index. The antitumor effects of the grain diets were associated with the activation of different mechanisms: immune response of the allergic type with augmented interleukin(IL)-9 and eotaxin serum levels in mice fed with control grain vs. inhibition of the IL-6/LIF system accompanied by a decrease in the tumor-associated M2 macrophage marker arginase 1 gene mRNA levels and enhanced autophagy in the tumor evaluated by the mRNA levels of Beclin 1 gene. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition with confirmed in vivo antitumor activity.

Characteristic features and prognostic factors in gastric cancer patients with bone metastases: multicenter experience

We evaluated the incidence, clinicopathological features, prognostic factors, progression-free survival (PFS) and overall survival (OS) of patients with gastric cancer and bone metastases. The medical records of 110 patients with bone metastases were retrospectively analyzed. In our study, the incidence of bone metastases was 3.2%. The median patient age was 60 years. A total of 68 (61.8%) patients exhibited synchronous metastases, and 42 (38.2%) patients developed metachronous metastases. Alkaline phosphatase (ALP) levels were high in 54 (49%) patients. At the median follow-up time of 9.8 months, median PFS and OS times were 4.7 and 6.3 months, respectively. The median interval from the diagnosis to bone metastases was 9.3 months. Univariate analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, use of zoledronic acid treatment, palliative chemotherapy post-bone metastases and radiotherapy to bone metastases were significant prognostic indicators for PFS. Additionally, ECOG PS ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, zoledronic acid treatment, palliative chemotherapy post-bone metastases, and radiotherapy to bone metastases significantly influenced OS. Moreover, in multivariate analysis, ECOG PS, time of metastases, presence of extra-bone metastases, and the use of palliative chemotherapy after bone metastases were found to be independent prognostic factors for PFS. Moreover, ECOG PS, time of metastases, and use of palliative chemotherapy after bone metastases were significantly independent prognostic indicators for OS. Our findings show that the presence of synchronous metastases, use of palliative chemotherapy, use of zoledronic acid after bone metastases, and ALP level within the normal range were significantly associated with prolonged OS in gastric cancer patients with bone metastases.

Analysis of survival rates and evaluation of prognostic factors in patients with lung metastases from renal cell carcinoma

In patients with lung metastases from renal cell cancer (RCC), it is necessary to search for new prognostic factors influencing survival rates. Aim: To analyze survival rates and identify prognostic factors in patients with lung metastases from RCC. Material and methods. We retrospectively analyzed the data from 655 patients with lung metastases from RCC, who were treated at Moscow city oncology Hospital No. 62 (Moscow) and city clinical oncology center (Saint Petersburg) from 2006 to 2022. Of these patients, 241 (36.8 %) were classified into the intermediate prognosis group, and 278 (42.2 %) into the unfavorable prognosis group. The study investigated clinical and morphologic prognostic factors influencing survival rates in patients with lung metastases from RCC. Statistical analysis was performed using Statistica 10.0 software packages (StatSoft, USA) by constructing Kaplan-Meier curves and survival tables, building a mathematical model of survival. Results. The 3- and 5-year OS rates in patients with lung metastases from RCC (N=655) were 48 % [95 % ci 45–53 %] and 27 % [95 % ci 23–31 %], respectively, with a median OS of 34.9 months [95 % ci 30.4–37.4]. in univariate analysis, ECOG status (p&lt;0.001), histological subtype (p&lt;0.001), Fuhrman grade of tumor differentiation (p&lt;0.001), type and number of metastases (p&lt;0.001), metastases to the bones and liver (p&lt;0.001), lymph nodes (p=0.001), prognosis according to IMDC(p&lt;0.001), nephrectomy and metastasectomy (p&lt;0.001) had a negative impact on OS in patients with lung metastases from RCC. In multivariate analysis, ECOG status 3.66 (2.10–6.39, p&lt;0.001), histological subtype 1.49 (1.10–2.01, p=0.009), grade of tumor differentiation according to Fuhrman 1.54 (1.13–2.09, p=0.006), number of metastases 3.63 (1.44–9.16, p=0.006), prognosis according to IMDC2.27 (1.63–3.17, p&lt;0.001), and nephrectomy 1.87 (1.29–2.70, p=0.001) and metastasectomy 0.69 (0.53–0.88, p=0.003) were additional factors influencing OS rates in patients with lung metastases from RCC. Conclusion. In our study, ECOG status, histologic subtype of RCC, Fuhrman grade of tumor differentiation, number of metastases, IMDC prognosis, and nephrectomy and metastasectomy were additional independent prognostic factors affecting OS in patients with lung metastases from RCC. Further studies are needed to investigate prognostic factors in patients with RCC lung metastases to improve the effectiveness of personalized treatment and survival rates.