Survival after pulmonary metastasectomy for relapsed osteosarcoma.

OBJECTIVES: The purpose of this study was to evaluate the postrelapse survival of relapsed osteosarcoma with pulmonary metastases in patients who received pulmonary metastasectomy using intent to treat and propensity score analysis. METHODS: Patients with osteosarcoma who relapsed with pulmonary metastases between 2004 and 2018 who were treated in a hospital affiliated with a medical school were included. All the enrolled patients were evaluated as operable with assessment algorithm at the time of diagnosis of pulmonary relapse and intent to treat analysis was done. Multiple propensity score methods (eg, matching, stratification, covariate adjustment, and inverse probability of treatment weighting) were performed to balance confounding bias. Cox proportional hazards regression and the Kaplan-Meier method were used to evaluate patient survival. RESULTS: A total of 125 patients met the study criteria. Of these, 59 (47.2%) patients received pulmonary metastasectomy combined with chemotherapy and 66 (52.8%) received chemotherapy alone. The 2-year and 5-year postrelapse survival rate of metastasectomy group and nonmetastasectomy group were 68.4% versus 25.0% and 41.0% versus 0%, respectively. The median postrelapse survival was 24.9 versus 13.5 months, respectively. Pulmonary metastasectomy was independently associated with improved survival (hazard ratio, 0.185; 95% confidence interval, 0.103-0.330; P < .001). These results were confirmed by multiple propensity score analyses. Further stratified analysis revealed that the survival advantage associated with metastasectomy was not significant in patients with metastases involving ≥3 lung lobes and patients with very high pretreatment serum alkaline phosphatase (more than twice the upper limit). CONCLUSIONS: Pulmonary metastasectomy is associated with improved survival in patients with recurrent osteosarcoma.

Impact of Intraoperative Blood Loss and Blood Transfusion on the Prognosis of Colorectal Liver Metastasis Following Curative Resection.

BACKGROUND/AIM: The identification of risk factors for recurrence after resection of colorectal liver metastasis is necessary in order to establish a more effective treatment strategy. In addition to well-known prognostic factors, such as the tumor diameter and number of metastatic tumors, a large amount of intraoperative blood loss (IBL) and blood transfusion have recently been reported to be associated with shorter long-term survival. The aim of this study was to assess the impact of IBL and blood transfusion on the prognosis of colorectal liver metastasis after curative resection. PATIENTS AND METHODS: A total of 104 patients who underwent R0 resection for colorectal liver metastasis were enrolled in this study. RESULTS: The high-IBL (>300 ml) group had significantly shorter relapse-free survival after hepatic resection in comparison to the low-IBL (≤300 ml) group (p=0.0025). Patients with blood transfusion had significantly shorter relapse-free survival after hepatic resection in comparison to patients without blood transfusion (p=0.0026). CONCLUSION: A large amount of IBL and blood transfusion may have a negative impact on long-term survival in patients who undergo hepatic resection for colorectal liver metastasis.

Stereotactic body radiation therapy for adrenal gland metastases: outcome and predictive factors from a multicenter analysis.

Adrenal metastases occur in 15-35% of oncological patients. Surgery is the first treatment option. Stereotactic body radiotherapy (SBRT) has been largely explored in oligometastatic patients unfit for surgery, representing an effective and non-invasive local treatment. The results of a multi-institutional experience of SBRT on adrenal metastases in the oligorecurrent or oligoprogressive setting are herein reported. We collected data of adrenal gland metastases treated with SBRT in three Italian centers from 2010 to 2020. End-points of the present study were: Overall survival (OS), Local control of treated metastases (LC), Progression free survival (PFS), and toxicity. 149 adrenal gland metastases were treated with SBRT in 142 patients. The most common primary tumor was lung cancer (58.4%), followed by kidney cancer (9.4%). Median lesion's volume was 28.5 cm3 (2.5-323.4). The median SBRT dose was 40 Gy (10-60). Median follow-up was 14.4 months. One- and two-year OS were 72.3% and 53.5%. At univariate analysis performance status correlated with survival (HR 1.57, p = 0.006). One- and two-year LC were 85.4% and 79.2%, with lung primary tumor (HR 0.33, p = 0.021) and BED10 (HR 0.97, p = 0.036) significant independent factors. One- and two-year PFS were 37.7% and 24.8%. Median time to polymetastatic disease was 11.3 months. Grade 1 and 2 toxicity occurred in 21 (14.7%) and 3 (2.1%) patients. The results from this large multi-center study confirm the efficacy and safety of SBRT in the management of adrenal gland metastases, as a valid alternative to other more invasive local approaches.

Treatments and Outcomes in Oligometastatic Soft Tissue Soft Sarcoma - A Single Centre Retrospective Analysis.

BACKGROUND/AIM: Distinguishing true oligometastatic disease from early polymetastatic disease is vital in patients with soft tissue sarcoma as contemporary treatment strategies differ significantly. Clinical factors such as tumour biology, organ involved, number of lesions, and patient fitness influence clinical decisions. PATIENTS AND METHODS: A retrospective search of a prospective database identified patients with new distant relapse, treated between 2009 and 2012. RESULTS: A total of 223 patients were included, and oligometastases were diagnosed in 81 (36%) patients, which were pulmonary in just over half of cases. These were treated with local therapy in 66 of 89 cases, and 7 patients received subsequent treatment for additional oligometastases. Metastasectomy was the most common treatment modality. A total of 16/66 patients (24%) underwent active surveillance for >6 months prior to local therapy. CONCLUSION: Patients with oligometastatic disease can experience durable disease control with timely multimodality treatment approaches for evolving metastatic disease, where disease biology allows.

Survival benefit of a combined surgical approach in patients with metastatic breast cancer.

BACKGROUND: We previously reported survival benefit of surgery in patients with stage IV breast cancer (BC); prospective trials yielded inconclusive results. METHODS: We sampled the National Cancer Database (2004-2016) for de novo stage IV BC patients undergoing both primary site resection and metastasectomy. A multivariate Cox-regression survival model investigated the overall survival (OS) of this surgical approach as compared to lumpectomy/mastectomy alone, metastasectomy alone, or no surgery. The Kaplan-Meier method was used to demonstrate the utility of surgery when metastasis were confined to 1 site stratifying by tissue type. RESULTS: A total of n = 55,125 patients were included. As compared to lumpectomy/mastectomy alone (43 months), lumpectomy/mastectomy + metastasectomy exhibited the best OS (50 months, p = 0.012), metastasectomy alone showed slightly worse OS (30 months, p < 0.0001), and no surgery had the worst OS (21 months, p < 0.0001). In metastasis confined to 1 site, superior OS with combined lumpectomy/mastectomy and metastasectomy versus lumpectomy/mastectomy alone was observed with liver (72.8 vs. 48.1 months, p < 0.001) or lung (49.2 vs. 36.8 months, p < 0.001) metastasis but not bone (52.2 vs. 49.9 months, p < 0.001) or brain (16.2 vs. 15.5 months, p < 0.001). CONCLUSION: Patients with metastatic BC undergoing primary site resection and metastasectomy exhibited optimal OS, particularly when metastasis involved only the liver or lung.

Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients.

BACKGROUND: The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population. METHODS: We identified 6708 young adults aged 18-45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan-Meier estimation, log rank test, and multivariate Cox proportional hazards model. RESULTS: Sixty-three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31-0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43-0.49, p < 0.001 and HR 0.64, 95% CI: 0.55-0.76, p < 0.001, respectively). CONCLUSION: This is the largest observational study to evaluate survival outcomes in young-onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.

The role of local therapy in the treatment of solitary melanoma progression on immune checkpoint inhibition: A multicentre retrospective analysis.

INTRODUCTION: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma. PATIENTS AND METHODS: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation. RESULTS: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n = 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n = 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p = 0.006), without OS differences. CONCLUSION: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes.

Video-assisted pulmonary metastectomy is equivalent to thoracotomy regarding resection status and survival.

BACKGROUND: Surgical resection of pulmonary metastases leads to prolonged survival if strictly indicated. Usually, thoracotomy with manual palpation of the entire lung with lymph node dissection or sampling is performed. The aim of this study was to evaluate the role of video-assisted thoracoscopic surgery (VATS) in pulmonary metastectomy with curative intent. METHODS: In this study, all patients with suspected pulmonary metastasis (n = 483) who visited the Center for Thoracic Surgery in Regensburg, between January 2009 and December 2017 were analysed retrospectively. RESULTS: A total of 251 patients underwent metastectomy with curative intent. VATS was performed in 63 (25.1%) patients, 54 (85.7%) of whom had a solitary metastasis. Wedge resection was the most performed procedure in patients treated with VATS (82.5%, n = 52) and thoracotomy (72.3%, n = 136). Postoperative revisions were necessary in nine patients (4.8%), and one patient died of pulmonary embolism after thoracotomy (0.5%). Patients were discharged significantly faster after VATS than after thoracotomy (p < 0.001). Complete (R0) resection was achieved in 89% of patients. The median recurrence-free survival was 11 months (95% confidence interval 7.9-14.1). During follow-up, eight (12.7%) patients in the VATS group and 42 (22.3%) patients in the thoracotomy group experienced recurrence (p = 0.98). The median overall survival was 61 months (95% confidence interval 46.1-75.9), and there was no significant difference with regard to the surgical method used (p = 0.34). CONCLUSIONS: VATS metastasectomy can be considered in patients with a solitary lung metastasis. An open surgical approach with palpation of the lung showed no advantage in terms of surgical outcome or survival.

Prognostic Value of Site-Specific Metastases and Therapeutic Roles of Surgery and Chemotherapy for Patients With Metastatic Renal Pelvis Cancer: A SEER Based Study.

BACKGROUND AND AIMS: There is a lack of research on metastatic renal pelvis cell carcinoma in the current literature. In this study, we aimed to detect distant metastatic patterns in renal pelvis cell carcinoma, and illustrated the affection of different metastatic sites, surgery to primary site and chemotherapy on prognosis outcomes in patients with diverse conditions. METHODS: We collected data between 2010 and 2015 from the Surveillance, Epidemiology and End Results database. Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 424 patients were included in the analysis, the median follow-up time was 5 months (interquartile range (IQR): 2-12) and 391 deaths (92.2%) in all patients were recorded. Among them, 192 (45.3%), 153 (36.1%), 137 (32.3%) and 127 (30.0%) patients were diagnosed with lung, bone, liver and brain metastases, respectively, while only 12 (2.8%) patients had brain metastases. The bi-organ, tri-organ and tetra-organ metastatic pattern was found in 135 (31.8%), 32 (7.5%) and 11 (2.6%) patients, respectively. The multivariate Cox analyses showed that distant lymph nodes (DL) metastases was not an independent prognostic factor for both OS and CSS (OS: Hazard ratios (HR) = 1.1, 95% CI = 0.8-1.4, P = 0.622; CSS: HR = 1.0, 95% CI = 0.8-1.3, P = 0.906). Besides, there was no significant difference of survival in patients with T3-T4 stage (OS: HR = 0.8, 95% CI = 0.5-1.2, P = 0.296; CSS: HR = 0.8, 95% CI = 0.5-1.2, P = 0.224), N2-3 stage (OS: HR = 0.8, 95% CI = 0.5-1.3, P = 0.351; CSS: HR = 0.7, 95% CI = 0.4-1.2, P = 0.259) and multi-organ metastases (OS: HR = 0.8, 95% CI = 0.5-1.3, P = 0.359; CSS: HR = 0.7, 95% CI = 0.4-1.2, P = 0.179) between surgery to primary site group and no-surgery to primary site group. CONCLUSION: we described the metastatic patterns of mRPCC and the prognosis outcomes of DL metastases, surgery to primary site and chemotherapy. Our findings provide more information for clinical therapeutic intervention and translational study designs.

Treatment Outcomes of Pulmonary Metastases from Head and Neck Squamous Cell Carcinoma.

Although the lung is the most common site of distant metastases from head and neck squamous cell carcinoma (HNSCC), the number of reports about the effects of pulmonary metastasectomy for the treatment of lung metastasis from HNSCC is limited. Metachronous pulmonary metastases were detected in 45 HNSCC patients at Kumamoto University Hospital from 1998 to 2018. Twenty-two patients underwent an operative resection (Ope group) and 23 underwent chemotherapy (Chemo group). The 3-year overall survival (OS) rate and median OS were evaluated. The effects of adjuvant chemotherapy after pulmonary metastasectomy and of new drugs (cetuximab and nivolumab), in the chemo group were also assessed. The 3-year OS rates and median OS were: Ope, 66.1% and 31.5 months; Chemo, 39.7% and 18 months, respectively. In the Ope group, addi-tional recurrences were significantly fewer in the patients who underwent adjuvant chemotherapy post-surgery versus the patients who underwent surgery alone (p = 0.013). In the Chemo group, the 3-year OS rate of the patients who received new drugs was significantly better than that of the patients who did not (p = 0.021). Adjuvant chemotherapy after pulmonary metastasectomy may be a preferable treatment option for preventing recurrences. Cetuximab and nivolumab have a potential to improve OS.

Current surgical management of children with osteosarcoma and pulmonary metastatic disease: A survey of the American Pediatric Surgical Association.

BACKGROUND: Rates of long-term survival for children with pulmonary metastatic osteosarcoma are low, and complete surgical resection of all visible pulmonary metastases is necessary for long term survival. Surgical approaches for metastasectomy include thoracotomy and thoracoscopy, with the approach chosen influenced by training and institutional bias. Thoracotomy with manual palpation of lung surfaces can identify nodules not seen on preoperative imaging, but no clear survival benefit has been demonstrated compared to complete thoracoscopic resection of all visible nodules. METHODS: All member of the American Pediatric Surgical Association were surveyed, and 204 members responded. RESULTS: Thoracoscopy was the preferred approach of 34% of surgeons for patients with 3 unilateral nodules but only 21% for those with 5 unilateral nodules. Hospital volume did not correlate with operative approach. Localization strategies are used by 37% of surgeons who prefer thoracotomy and 64% who prefer thoracoscopy. Importantly, the vast majority of responding surgeons (84%) expressed a willingness to participate in a randomized controlled trial of thoracotomy versus thoracoscopy. CONCLUSION: Findings of this survey of North American pediatric surgeons confirm both the need for, and interest in, a prospective trial to define optimal surgical management of children with osteosarcoma with limited pulmonary metastasis. LEVEL OF EVIDENCE: V.

Pulmonary Metastasectomy in Colorectal Cancer: A Population-Based Retrospective Cohort Study Using the Korean National Health Insurance Database.

PURPOSE: The study aimed to investigate the current status and prognostic factors for overall survival in patients who had undergone pulmonary metastasectomy for colorectal cancer. MATERIALS AND METHODS: The data of 2,573 patients who had undergone pulmonary metastasectomy after surgery for colorectal cancer between January 2009 and December 2014 were extracted from the Korean National Health Insurance Service claims database. Patient-, colorectal cancer-, pulmonary metastasis-, and hospital-related factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis to identify prognostic factors for overall survival after pulmonary metastasectomy. RESULTS: The mean age of the patients was 60.9±10.5 years; 66.2% and 79.1% of the participants were male and had distally located colorectal cancer, respectively. Wedge resection (71.7%) was the most frequent extent of pulmonary resection; 21.8% of the patients underwent repeated pulmonary metastasectomies; 73% of pulmonary metastasectomy cases were performed in tertiary hospitals; 53.9% of patients were treated in Seoul area; 82% of patients received chemotherapy in conjunction with pulmonary metastasectomy. The median survival duration was 51.8 months. The 3- and 5-year overall survival rates were 67.7% and 39.4%, respectively. In multivariate analysis, female sex, distally located colorectal cancer, pulmonary metastasectomy-only treatment, and high hospital volume (> 10 pulmonary metastasectomy cases/yr) were positive prognostic factors for survival. CONCLUSION: Pulmonary metastasectomy seemed to provide long-term survival of patients with colorectal cancer. The female sex, presence of distally located colorectal cancer, and performance of pulmonary metastasectomy in high-volume centers were positive prognostic factors for survival.

Pathologic concordance of resected metastatic nonseminomatous germ cell tumors in the chest.

OBJECTIVE: Men with metastatic nonseminomatous germ cell tumors (NSGCTs) often present with residual chest tumors after chemotherapy. We examined the pathologic concordance of intrathoracic disease and outcomes based on the worst pathology of disease resected at first thoracic surgery. METHODS: A retrospective analysis was performed of consecutive patients undergoing thoracic resection for metastatic NSGCT in our institution between 2005 and 2018. RESULTS: Eighty-nine patients (all men) were included. The median age was 29 years (interquartile range [IQR], 23-35 years). Primary sites were testis (n = 84; 94.4%) and retroperitoneum (n = 5; 5.6%). Eighty-seven patients received chemotherapy before undergoing surgery. Nineteen patients (21.3%; group 1) had malignancy resected at first surgery (OR1), and the other 70 patients had benign disease at OR1 (78.7%; group 2). Concordant pathology between lungs was 85.2% in group 1 and 91% in group 2, and between lung and mediastinum was 50% in group 1 and 72.7% in group 2. Despite no teratoma at OR1, 3 patients (15.8%) in group 2 had resection of teratoma (n = 2) or malignancy (n = 1) at future surgery. After a mean follow-up of 65.5 months (IQR, 23.1-89.2 months) for group 1 and 47.7 months (IQR, 13.0-75.1 months) for group 2, overall survival was significantly worse for group 1 (68.4% vs 92.9%; P = .03). CONCLUSIONS: The wide range of pathology resected in patients with intrathoracic NSGCT metastases requires careful decision making regarding treatment. Pathologic concordance between lungs is better than that between lung and mediastinum in patients with intrathoracic NSGCT metastases. Aggressive surgical management should be considered for all residual disease due to the low concordance between sites and the potential for excellent long-term survival even in patients with chemotherapy-refractory disease.

Is resection for noncolorectal, nonneuroendocrine liver metastases justified?

INTRODUCTION: The role of hepatectomy in non-colorectal, nonneuroendocrine liver metastasis (NCNN) is not clearly defined. This study represents a step towards surgical frame-shift as an integral part of treatment pathway in these heterogeneous, arbitrarily treated tumors. It aims to provide answers regarding favorable tumor types and patient profiles for which liver metastasectomy would prove beneficial. MATERIALS AND METHODS: Retrospective analysis of prospectively maintained database of hepatectomy in NCNN liver metastasis. RESULTS: A total of 50 patients out of 516 patients underwent liver resection during this period. In 27 patients, the liver metastases presented synchronously whereas the other 23 were metachronous. Median disease-free interval (DFI) was 36 months. Gastrointestinal stromal tumors (GIST) were the most common type of primary malignancy (15, 30%). In 41 patients, the liver was the only site of metastases. At a median follow-up of 32.5 months, 24 patients developed recurrences. Five-year overall (OS) and disease-free survival (DFS) for the entire cohort was 60% and 32%, respectively. Median OS was highest in the breast (93 months) followed by GIST (56 months). Patients with longer DFI showed improved OS. (p = .04). CONCLUSION: Liver resection for NCNN metastases is safe and feasible in selected patients with good survival outcomes. Longer DFI correlates with better survival.

Clinical significance of RBM3 expression in surgically treated colorectal lung metastases and paired primary tumors.

BACKGROUND: The lungs are the second most common site of metastases in colorectal cancer (CRC). The aim of this study was to investigate prognostic factors, including RNA-binding motif protein 3 (RBM3) expression, in patients with CRC treated with pulmonary metastasectomy (PM). METHODS: The cohort included all patients treated with PM at Skåne University Hospital, Lund, Sweden, from 2000 to 2014. Clinicopathological, treatment, and survival data were collected. Immunohistochemical staining of RBM3 was evaluated on tissue microarrays with samples from all lung metastases and a subset of paired primary tumors. Kaplan-Meier analysis and Cox proportional hazards modeling were applied to examine the associations of investigative factors with overall survival (OS) and recurrence-free survival. RESULTS: In total, 216 patients with a primary tumor in the rectum (57%), left colon (34%), or right colon (9%) underwent PM. The 5-year OS rate was 56%. Age > 60 years, more than one metastasis, size of metastasis > 3 cm, disease-free interval < 24 months, low RBM3 score in the lung metastasis, and no adjuvant chemotherapy following PM were prognostic factors for shorter OS. CONCLUSIONS: Several prognostic factors, including RBM3 expression, may be of aid in selecting CRC patients with lung metastases for PM as well as adjuvant therapy.

Metastatic renal cell carcinoma to the pancreas: Clinical features and treatment outcome.

BACKGROUND AND OBJECTIVES: Metastatic renal cell carcinoma to the pancreas (PM-RCC) is infrequent; we sought to describe the characteristics of PM-RCC and analyze the outcome following treatment. METHODS: Data of 3107 mRCC patients treated between 1992 and 2007 from the Korean Renal Cancer Study Group database were obtained to identify 300 (9.7%) PM-RCC patients. Characteristics and survival were analyzed and compared to the rest of the mRCC, according to the timing of metastasis and surgical treatments received. RESULTS: PM-RCC was younger at initial diagnosis (55.0 vs. 58.2 years), more frequently in women (30.3% vs. 22.3%), and metachronous (65.3% vs. 41.9%) with a longer disease-free period (82.0 vs. 33.0 months). Overall survival (OS) was significantly better in PM-RCC but pancreas metastasectomy was associated with improved OS only among metachronous PM-RCC. In the 132 metachronous PM-RCC with pancreas metastasectomy, median recurrence-free survival was 17.2 months and we found Heng risk group (hazard ratio [HR] = 2.384, 95% confidence interval [CI] = 1.213-4.684), younger age (HR = 0.965, 95% CI = 0.945-0.987), shorter interval to pancreas metastasis (HR = 0.993, 95% CI = 0.986-0.999), and Eastern Cooperative Oncology Group performance status to be predictive of early progression following pancreas metastasectomy. CONCLUSION: Compared to the other mRCC, PM-RCC demonstrated a favorable prognosis. Pancreas metastasectomy was associated with prolonged survival in the metachronous PM-RCC with a long progression-free period.