Multiplexed analysis of macrophage polarisation in pulmonary metastases of microsatellite stable colorectal cancer.

Tumour-associated macrophages (TAMs) express a continuum of phenotypes ranging from an anti-tumoural M1-like phenotype to a pro-tumoural M2-like phenotype. During cancer progression, TAMs may shift to a more M2-like polarisation state, but the role of TAMs in CRC metastases is unclear. We conducted a comprehensive spatial and prognostic analysis of TAMs in CRC pulmonary metastases and corresponding primary tumours using multiplexed immunohistochemistry and machine learning-based image analysis. We obtained data from 106 resected pulmonary metastases and 74 corresponding primary tumours. TAMs in the resected pulmonary metastases were located closer to the cancer cells and presented a more M2-like polarised state in comparison to the primary tumours. Higher stromal M2-like macrophage densities in the invasive margin of pulmonary metastases were associated with worse 5-year overall survival (HR 3.19, 95% CI 1.35-7.55, p = 0.008). The results of this study highlight the value of multiplexed analysis of macrophage polarisation in cancer metastases and might have clinical implications in future cancer therapy.

Let it glow: Intraoperative visualization of pulmonary metastases using pafolacianine, a next-generation fluorescent agent, for young adults undergoing pulmonary metastasectomy.

A new generation of disease-specific molecular imaging agents is poised to revolutionize fluorescence-guided surgery. Pafolacianine has been approved for adult lung and ovarian cancers. We demonstrate a proof of concept for pediatric surgeons treating young adults with pulmonary metastatic sarcomas. Five successful fluorescence-guided pulmonary metastasectomy operations were performed in young adult patients with metastatic osteosarcoma or Ewing sarcoma following administration of pafolacianine. All osteosarcoma lesions identified using standard techniques were also markedly fluorescent in patients. Novel fluorescent molecular agents targeted to tumor-specific receptors have promise of increased sensitivity and specificity for detecting metastatic nodules and enhancing surgical clearance of disease.

Predictors of pulmonary metastases on chest computed tomography in children and adolescents with osteosarcoma-tips for qualifying patients for thoracotomy.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Lungs are the most frequent and often the only site of metastatic disease. The presence of pulmonary metastases is a significant unfavourable prognostic factor. Thoracotomy is strongly recommended in these patients, while computed tomography (CT) remains the gold imaging standard. The purpose of our study was to create tools for the CT-based qualification for thoracotomy in osteosarcoma patients in order to reduce the rate of useless thoracotomies. METHODS: Sixty-four osteosarcoma paediatric patients suspected of lung metastases on CT and their first-time thoracotomies (n = 100) were included in this retrospective analysis. All CT scans were analysed using a compartmental evaluation method based on the number and size of nodules. Calcification and location of lung lesions were also analysed. Inter-observer reliability between two experienced radiologists was assessed. The CT findings were then correlated with the histopathological results of thoracotomies. Various multivariate predictive models (logistic regression, classification tree and random forest) were built and predictors of lung metastases were identified. RESULTS: All applied models proved that calcified nodules on the preoperative CT scan best predict the presence of pulmonary metastases. The rating of the operated lung on the preoperative CT scan, dependent on the number and size of nodules, and the total number of nodules on this scan were also found to be important predictors. All three models achieved a relatively high sensitivity (72-92%), positive predictive value (81-90%) and accuracy (74-79%). The positive predictive value of each model was higher than of the qualification for thoracotomy performed at the time of treatment. Inter-observer reliability was at least substantial for qualitative variables and excellent for quantitative variables. CONCLUSIONS: The multivariate models built and tested in our study may be useful in the qualification of osteosarcoma patients for metastasectomy through thoracotomy and may contribute to reducing the rate of unnecessary invasive procedures in the future.

Salvage surgery for local recurrences after stereotactic ablative radiotherapy of colorectal pulmonary metastases.

INTRODUCTION: Local control following stereotactic ablative radiotherapy (SABR) for patients with colorectal pulmonary metastases is reportedly lower than for metastases from other tumors. Such recurrences may still be amenable to salvage therapy. We describe our experience with salvage surgery in 17 patients. METHODS: Patients who underwent salvage metastasectomy for a local recurrence following SABR for colorectal pulmonary metastases were identified from the surgical institutional databases of three Dutch major referral hospitals. Kaplan-Meier survival analysis was performed to determine survival. RESULTS: Seventeen patients underwent 20 salvage resections for local recurrence of colorectal pulmonary metastases. All patients had a progressive lesion on consecutive CT scans, with local uptake on 18 fluorodeoxyglucose-positron emission tomography computed tomography (FDG-PET CT), and were discussed in a thoracic oncology tumor board. Median time to local recurrence following SABR was 20 months (interquartile range [IQR]: 13-29). Fourteen procedures were performed minimally invasively. Extensive adhesions were observed during three procedures. A Clavien-Dindo grade III-IV complication occurred after four resections (20%). The 90-day mortality was 0%. The estimated median overall survival and progression-free survival following salvage resection were 71 months (confidence intervals [CI]: 50-92) and 39 months (CI: 19-58), respectively. Salvage resections were significantly more extensive, compared to the potential resection assessed on pre-SABR imaging. CONCLUSIONS: Our experience with 20 salvage pulmonary metastasectomy procedures for local recurrences following SABR in colorectal cancer patients demonstrates that salvage resection is a feasible option with acceptable morbidity and good oncological outcome in a highly selected cohort.

Curative-intent treatment of pulmonary metastases from colorectal cancer: A comparison between imaging-guided thermal ablation and surgery.

BACKGROUND: Pulmonary metastases (PM) are the most frequent extra-abdominal metastases from colorectal cancer. Lung resection and imaging-guided thermal ablation (IGTA) are used as curative-intent treatment. We compared the outcomes of patients with PM, treated with resection or ablation. METHODS: We retrospectively analyzed data from patients who underwent surgery or IGTA for colorectal PM between April 2011 and November 2020. Surgery was performed for peripheral PM and IGTA for deep-located PM not in contact with major vessels. Patients who had both procedures were excluded. Patients were compared using propensity score matching (PSM) analysis, stratified according to number, size, and unilaterality of PM. RESULTS: One hundred and fourty-six patients were included, 65 (44.5%) underwent surgery and 81 (55.5%) underwent IGTA. After PSM analysis, each group contained 46 patients. IGTA patients had a lower morbidity rate (13.1% vs. 15.2%, p = 0.028) and a shorter length of stay (5.13 vs. 2.63 days, p < 0.001). Oncological outcomes were similar in both groups with 5-year OS of 80% and 5-year progression-free survival (PFS) of 30% (p = 0.657 and p = 0.504, respectively) with similar recurrence patterns. CONCLUSION: Lung resection and IGTA seem to have similar oncologic outcomes for both OS and PFS. IGTA could be an alternative effective treatment for small PM, whenever technically feasible.

Feasibility of indocyanine green-guided localization of pulmonary nodules in children with solid tumors.

BACKGROUND: Clearing all pulmonary metastases is essential for curing pediatric solid tumors. However, intraoperative localization of such pulmonary nodules can be challenging. Therefore, an intraoperative tool that localizes pulmonary metastases is needed to improve diagnostic and therapeutic resections. Indocyanine green (ICG) real-time fluorescence imaging is used for this purpose in adult solid tumors, but its utility in pediatric solid tumors has not been determined. METHODS: A single-center, open-label, nonrandomized, prospective clinical trial (NCT04084067) was conducted to assess the ability of ICG to localize pulmonary metastases of pediatric solid tumors. Patients with pulmonary lesions who required resection, either for therapeutic or diagnostic intent, were included. Patients received a 15-minute intravenous infusion of ICG (1.5 mg/kg), and pulmonary metastasectomy was performed the following day. A near-infrared spectroscopy iridium system was optimized to detect ICG, and all procedures were photo-documented and recorded. RESULTS: ICG-guided pulmonary metastasectomies were performed in 12 patients (median age: 10.5 years). A total of 79 nodules were visualized, 13 of which were not detected by preoperative imaging. Histologic examination confirmed the following histologies: hepatoblastoma (n = 3), osteosarcoma (n = 2), and one each of rhabdomyosarcoma, Ewing sarcoma, inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, and papillary thyroid carcinoma. ICG guidance failed to localize pulmonary metastases in five (42%) patients who had inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, or papillary thyroid carcinoma. CONCLUSIONS: ICG-guided identification of pulmonary nodules is not feasible for all pediatric solid tumors. However, it may localize most metastatic hepatic tumors and high-grade sarcomas in children.

Benign metastasizing uterine leiomyoma with lymphatic and pulmonary metastases: a case report and literature review.

BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare disease usually observed in women of reproductive or premenopausal age with a history of uterine myomectomy or hysterectomy. The most common sites of metastases are the pulmonary, and other sites include heart, bones, liver, lymph nodes, bladder, skeletal muscles, and central nervous system. Here, we report a case of a 50 year-old woman with a history of hysterectomy who was initially suspected of uterine sarcoma but was finally confirmed to have BML with lung and lymph node metastases, and discuss the treatment and prognosis of BML. CASE PRESENTATION: A 50 year-old woman with a history of total abdominal hysterectomy presented with mild but persistent abdominal pain for more than 3 months. She was suspected of having uterine sarcoma before surgery and laparoscopic extensive debulking surgery including bilateral oophorectomy, pelvic and para-aortic lymph node dissection to the level of the left renal vein, and transcutaneous dissection of the right inguinal lymph nodes. Pathology confirmed a benign leiomyoma, and the patient was diagnosed with BML. No medication was administered after the surgery, and the follow-up was of no significance. CONCLUSION: Benign metastasizing leiomyoma (BML) is a rare disorder in which histologically benign smooth muscle tumors metastasize to extrauterine sites. Metastases are commonly observed in the lung, liver, lymph nodes, skin, bladder, esophagus, and skeletal muscles. BML is usually misdiagnosed as a malignant tumor before surgery until the pathology confirms its benign nature. However, this treatment remains controversial and undetermined. The prognosis is usually favorable owing to its benign nature.

Radiomics analysis based on CT for the prediction of pulmonary metastases in ewing sarcoma.

OBJECTIVES: This study aimed to develop and validate radiomics models on the basis of computed tomography (CT) and clinical features for the prediction of pulmonary metastases (MT) in patients with Ewing sarcoma (ES) within 2 years after diagnosis. MATERIALS AND METHODS: A total of 143 patients with a histopathological diagnosis of ES were enrolled in this study (114 in the training cohort and 29 in the validation cohort). The regions of interest (ROIs) were handcrafted along the boundary of each tumor on the CT and CT-enhanced (CTE) images, and radiomic features were extracted. Six different models were built, including three radiomics models (CT, CTE and ComB models) and three clinical-radiomics models (CT_clinical, CTE_clinical and ComB_clinical models). The area under the receiver operating characteristic curve (AUC), and accuracy were calculated to evaluate the different models, and DeLong test was used to compare the AUCs of the models. RESULTS: Among the clinical risk factors, the therapeutic method had significant differences between the MT and non-MT groups (P＜0.01). The six models performed well in predicting pulmonary metastases in patients with ES, and the ComB model (AUC: 0.866/0.852 in training/validation cohort) achieved the highest AUC among the six models. However, no statistically significant difference was observed between the AUC of the models. CONCLUSIONS: In patients with ES, clinical-radiomics model created using radiomics signature and clinical features provided favorable ability and accuracy for pulmonary metastases prediction.

CT-guided percutaneous microwave ablation for pulmonary metastases from colorectal cancer: Prognosis analyses based on the origin of the primary tumor.

BACKGROUND: Microwave ablation (MWA) is becoming an effective therapy for inoperable pulmonary metastases from colorectal cancer (CRC). However, it is unclear whether the primary tumor location affects survival after MWA. OBJECTIVE: This study aims to investigate the survival outcomes and prognostic factors of MWA based on different primary origins between colon and rectal cancer. METHODS: Patients who underwent MWA for pulmonary metastases from 2014 to 2021 were reviewed. Differences in survival outcomes between colon and rectal cancer were analyzed with the Kaplan-Meier method and log-rank tests. The prognostic factors between groups were then evaluated by univariable and multivariable Cox regression analyses. RESULTS: A total of 118 patients with 154 pulmonary metastases from CRC were treated in 140 MWA sessions. Rectal cancer had a higher proportion with seventy (59.32% ) than colon cancer with forty-eight (40.68% ). The average maximum diameter of pulmonary metastases from rectal cancer (1.09 cm) was greater than that of colon cancer (0.89 cm; p = 0.026). The median follow-up was 18.53 months (range 1.10 - 60.63 months). The disease-free survival (DFS) and overall survival (OS) in colon and rectal cancer groups were 25.97 vs 11.90 months (p = 0.405), and 60.63 vs 53.87 months (p = 0.149), respectively. Multivariate analyses showed that only age was an independent prognostic factor in patients with rectal cancer (HR = 3.70, 95% CI: 1.28 - 10.72, p = 0.023), while none in colon cancer. CONCLUSIONS: Primary CRC location has no impact on survival for patients with pulmonary metastases after MWA, while a disparate prognostic factor exists between colon and rectal cancer.

Preoperative PDW levels predict pulmonary metastasis in patients with hepatocellular carcinoma.

BACKGROUND: In hepatocellular carcinoma (HCC), pulmonary metastasis (PM) after hepatectomy is associated with poor clinical outcomes. The crucial phases of tumour cell proliferation, angiogenesis, and metastasis all entail platelet activation. In HCC, platelet distribution width (PDW) suggests platelet size changes and predicts a worse prognosis. The aim of this study was to assess the association between PDW and PMs in HCC patients receiving hepatectomy. MATERIAL/METHODS: From January 2013 to December 2015, a cohort of patients who underwent hepatectomy for HCC at the Harbin Medical University Cancer Hospital in China were retrospectively evaluated. The relationship between PDW levels and clinical and demographic parameters was examined. To investigate the relationships between predicted factors and PM, a competing risk model was used. From January 2016 to December 2018, a validation cohort of 109 patients from the First Affiliated Hospital of Harbin Medical University was studied independently. RESULTS: In the primary cohort, 19 out of 214 patients had postoperative PMs. In HCC patients with PM, PDW levels were lower than in those without PM. There was a significant difference in the cumulative incidence of 2-year PM between the high-PDW and low-PDW groups after controlling for competing risk events (death prior to the development of PM) (p < 0.001). In addition, PDW was also found to be an independent predictor for PM in a multivariable competing risk analysis. The results were externally validated in another cohort. CONCLUSIONS: In HCC, preoperative PDW is significantly associated with PM. PDW could be a biomarker for post-operative PM in HCC patients.

Low incidence of pulmonary metastases in vulvar cancer patients: limited value of routine chest imaging based on a cohort study.

OBJECTIVE: To evaluate the incidence of pulmonary metastases in the preoperative work-up of patients with primary vulvar squamous cell carcinoma (SCC). DESIGN: Retrospective cohort study. SETTING: Tertiary referral centre. POPULATION: Patients treated for primary vulvar SCC from 2000 to 2018. METHODS: The pre-operative chest imaging of 452 consecutively treated patients was documented with a minimal follow-up period of 2 years. MEAN OUTCOME MEASURES: Incidence of pulmonary metastases, frequency of chest imaging and subsequent coincidental findings. RESULTS: In total, 80.8% of patients underwent pre-operative chest imaging. Seven patients (1.9%), with a median tumour size of 80 mm, presented with pulmonary metastases. None of the patients with early stage disease and tumour size <40 mm who underwent radical local excision (RLE) with sentinel node (SN)-procedure, was diagnosed with pulmonary metastasis. Chest imaging was performed by radiography (58.9%) and computerised tomography (CT) (41.1%). Coincidental findings were reported in 40.7% of patients who underwent CT, compared with 15.8% of patients undergoing radiography, resulting in additional diagnostics in 14.7 and 19.7% and being of limited consequence for outcome in 2.9 and 3.3%, respectively. CONCLUSIONS: The incidence of pulmonary metastases in patients with primary vulvar SCC is extremely low, and none in patients with early stage disease undergoing the SN procedure. Chest imaging was performed in the majority of patients and was associated with frequent coincidental findings leading to clinically irrelevant diagnostic procedures. Therefore, we recommend omitting chest imaging in patients with early stage disease and tumours <40 mm, considering chest CT only in patients with large tumours and/or advanced stage disease. TWEETABLE ABSTRACT: The incidence of pulmonary metastases is 1.9%, none in early stage disease planned for SN. Omitting chest imaging in this group is advised.

Pneumothorax caused by metastatic gestational trophoblastic neoplasia: a case report.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) is a group of malignant neoplasms that arise from abnormal proliferation of trophoblastic tissue. The metastatic spread rate is depended on the histopathological type, with pulmonary metastases being the most common (80%) in patients with metastases. Pneumothorax as a primary manifestation is extremely rare. We hereby discuss a unique case of spontaneous hemi-pneumothorax due to metastatic GTN in a 30-weeks pregnant woman. CASE PRESENTATION: A 25-year-old woman - G2 P0 A1 - was admitted to our maternal intensive care department with atypical respiratory symptoms. A chest x-ray revealed a large right sided pneumothorax. The patient underwent an urgent percutaneous chest tube. Since halting of the suction resulted in residual pneumothorax, a video-assisted thoracoscopic surgery (VATS) with wig resection of a bullous lesion was performed followed by chemical pleurodesis. Histopathological examination identified the lesion as a gestational trophoblastic metastasis with some features of choriocarcinoma. After primary section Caesarea adjuvant chemotherapy (MTX) was instigated with rapid decline of serum HCG values. Six months after surgery she was doing well with no biochemical or radiographic evidence of recurrent metastasis. CONCLUSION: Lung metastases are common in patients with metastatic GTN; however, pneumothorax is an extremely rare complication. We report a case of pneumothorax in a 30-week pregnant woman caused by pulmonary spread of GTN from a previous miscarriage. This case illustrates that in patients with pneumothorax and a history of miscarriage, metastatic GTN should be considered as a possible cause.

Interstitial single fraction brachytherapy for malignant pulmonary tumours.

PURPOSE: Interstitial brachytherapy for pulmonary tumours is an alternative to stereotactic radiotherapy, allowing high conformity despite it being an invasive technique. The aim of the study was the analysis of dose distribution, toxicity and tumour response rates. METHODS: In the years 2014-2019, 27 patients with pulmonary tumours received 36 interstitial brachytherapies with Ir-192: 11 patients with non-small cell lung cancer, 16 patients with pulmonary metastases of other entities. RESULTS: Patients were treated with a median (interquartile range) prescription dose of 20 (20-26) Gy in a single fraction. Mean lung dose to the ipsilateral lung was 2.8 (1.6-4.7) Gy. Maximum doses to the heart, oesophagus, thoracic wall and spinal cord were 2.4 (1.8-4.6) Gy, 2.0 (1.2-6.2) Gy, 12.6 (8.0-18.2) Gy and 1.5 (0.6-3.9) Gy. Median survival after treatment was 15 months, with a 1- and 2­year local control of 84% and 60%. Median overall survival after initial cancer diagnosis was 94 months; 2 years following brachytherapy, 75% of patients with colorectal cancer vs. 37% with other histologies were alive; p = 0.14. In 69% (n = 25), brachytherapy could be performed without acute complications. A self-limiting bleeding occurred in 8% (n = 3), fever in 3% (n = 1), pneumothorax in 17% (n = 6), and pulmonary failure in 3% (n = 1). Patients with > 20 Gy in 95% of planning target volume had higher pneumothorax rates needing intervention (31% vs. 5%, p = 0.04). CONCLUSIONS: Interstitial brachytherapy for pulmonary tumours is a highly conformal therapy with minimal doses to the organs at risk. For the majority of patients, treatment can be performed without relevant complications in a single fraction with a satisfactory local control.

Dose coverage impacts local control in ultra-central lung oligometastases treated with stereotactic radiotherapy.

INTRODUCTION: The use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is to assess the determinants of efficacy and toxicity in this setting. MATERIALS AND METHODS: Clinical and dosimetric parameters were reviewed in a cohort of oligometastatic patients treated with SBRT for ultra-central tumors. Local control rate (LC) and toxicity were assessed. Statistical Analysis was carried out to assess the impact of those predictors on local recurrence and adverse events. RESULTS: One-hundred-nine consecutive patients were included. A median Biologic Effective Dose (BED) of 105 (75-132) Gy10 was prescribed. At a median follow-up of 17 (range 3-78) months, 2-year LC was 87%. Improved LC was correlated to Planning Treatment Volume (PTV) covered by 95% of the prescription dose (V95% PTV) > 85% (HR 0.15, 95%CI 0.05-0.49, p = 0.0017) and to Gross Tumor Volume (GTV) < 90 cm3 (HR 0.2, 95%CI 0.07-0.56, p = 0.0021). Overall and grade ≥ 3 toxicity incidence was 20% and 5%, respectively. Patients experiencing acute and late toxicities received significantly higher dose to 1 cm3 (D1cm3) of esophagus and lung volume receiving ≥5 Gy (V5Gy) (p = 0.016 and p = 0.013), and higher dose to 0.1 cm3 (D0.1cm3) of heart (p = 0.036), respectively. CONCLUSION: V95% PTV > 85% and GTV < 90 cm3 are independent predictors of LC. Dose to esophagus, lung and heart should be carefully assessed to minimize treatment-related toxicities.

The impact of primary tumor location on prognosis after colorectal lung metastasectomy.

PURPOSE: Currently, right colon cancer (RCC), left colon cancer (LCC), and rectal cancer (REC) are typically seen as different tumor entities. It is unknown if this subdivision by primary tumor location has an influence on the survival of patients with colorectal pulmonary metastasectomy (PM). METHODS: We retrospectively analyzed our prospective database of 233 patients operated on for colorectal lung metastases between 1999 and 2014. Differences in the patient characteristics and the primary tumor and metastatic tumor burden were analyzed using χ2-tests. The long-term survival after PM of the three groups was analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: In total, PM was performed for 37 patients with RCC, 57 patients with LCC, and 139 patients with REC. Patients with LCC were significantly more likely to have UICC stage IV primary tumor (44.2% LCC vs. 37.5% RCC vs. 22.8% REC, p = 0.012) and significantly more likely to have a history of additional liver metastases (45.6% LCC vs. 32.4% RCC vs. 27.3% REC, p = 0.046). The 5-year survival rates after PM for patients with RCC, LCC, and REC were 47, 66, and 39%, respectively (p = 0.001). The median survival times of patients with RCC, LCC, and REC were 55 months (95% CI: 42.2-66.8), 108 months (95% CI: 52.7-163.3), and 44 months (95% CI: 50.4-63.6), respectively. CONCLUSIONS: This study demonstrated a prognostic impact of the primary tumor localization in patients undergoing PM for colorectal lung metastases. Nevertheless, long-term survival was achievable in all groups.

The second modification of a dedicated staging system for lung metastases.

The topic of pulmonary metastases has long been of high interest and ongoing controversy. There is a group of patients with pulmonary metastases who may benefit from curative resection. It remains unclear which among them will benefit from surgery in terms of survival. This work updates a previously proposed classification system for pulmonary metastases, similar in its essence to the tumor, nodes, metastasis (TNM) classification used for primary tumors and named pmTNM classification, where 'pm' stands for 'pulmonary metastasis'. The objective is to allow future studies to explore predictive and survival prognostic factors for pulmonary metastases and separate patients who will benefit from lung metastasectomy from those who will not. The secondary aim is to provide a classification system that will allow physicians, oncologists and surgeons to speak the same language in comparing their data and assessing the results of treatment of lung metastases.

National variation in pulmonary metastasectomy for colorectal cancer.

AIM: Evidence on patterns of use of pulmonary metastasectomy in colorectal cancer patients is limited. This population-based study aims to investigate the use of pulmonary metastasectomy in the colorectal cancer population across the English National Health Service (NHS) and quantify the extent of any variations in practice and outcome. METHODS: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2013 were identified in the COloRECTal cancer data Repository (CORECT-R). All inpatient episodes corresponding to pulmonary metastasectomy, occurring within 3 years of the initial colorectal resection, were identified. Multi-level logistic regression was used to determine patient and organizational factors associated with the use of pulmonary metastasectomy for colorectal cancer, and Kaplan-Meier and Cox models were used to assess survival following pulmonary metastasectomy. RESULTS: In all, 173 354 individuals had a major colorectal resection over the study period, with 3434 (2.0%) undergoing pulmonary resection within 3 years. The frequency of pulmonary metastasectomy increased from 1.2% of patients undergoing major colorectal resection in 2005 to 2.3% in 2013. Significant variation was observed across hospital providers in the risk-adjusted rates of pulmonary metastasectomy (0.0%-6.8% of patients). Overall 5-year survival following pulmonary resection was 50.8%, with 30-day and 90-day mortality of 0.6% and 1.2% respectively. CONCLUSIONS: This study shows significant variation in the rates of pulmonary metastasectomy for colorectal cancer across the English NHS.

Skip metastases in high-grade intramedullary appendicular osteosarcoma: an indicator of more aggressive disease?

OBJECTIVE: To determine whether skip metastases (SM) in high-grade appendicular osteosarcoma (HG-OS) are an indicator of more aggressive disease. MATERIALS AND METHOD: Retrospective review of patients with histologically confirmed diagnosis HG-OS of the long bones from 2007 to 2020, who had whole-bone MRI to identify SM. Data collected included patient age/gender, bone involved, the presence of SM, the presence of lung metastases from chest CT, the presence of distant bone metastases from whole-body bone scintigraphy or whole-body MRI, and chemotherapy response from resection specimen histology. The presence of lung or bone metastases and chemotherapy response were compared between patients without and with SM. RESULTS: The study included 241 patients (146 males; 95 females: mean age 18.2 years; range 4-73 years). Based on whole-bone MRI, 202 (83.8%) patients had no SM and 39 (16.2%) patients had a SM. Of patients without a SM, lung metastases were identified in 44 (22%) and distant bone metastases in 6 (3%) cases, while 80 (43%) had a good chemotherapy response and 105 (57%) had a poor chemotherapy response. Of patients with a SM, lung metastases were identified in 22 (58%) and distant bone metastases in 8 (21%) cases, while 11 (32%) had a good chemotherapy response and 23 (68%) had a poor chemotherapy response. The presence of SM was significantly associated with both lung metastases (p < 0.001) and skeletal metastases (p < 0.001), but not with chemotherapy response (p = 0.24). Patients with SM also had poorer survival (p < 0.001). CONCLUSIONS: The presence of SM in appendicular HG-OS suggests more aggressive disease.

Site of relapse of ductal adenocarcinoma of the pancreas affects survival after multimodal therapy.

BACKGROUND: Ductal adenocarcinoma of the pancreas (PDAC) remains one of the most lethal malignancies. To date, no guidelines exists for isolated resectable metachronous disease. It is still unknown, which patients may benefit from relapse surgery. The aim of our study was to compare disease free survival (DFS) and post relapse survival (PRS) in patients with isolated local recurrence, metachronous hepatic or pulmonary metastases. METHODS: Patients with isolated resectable local recurrence, metachronous hepatic or pulmonary metastases were included for survival analyses. PRS of surgically treated patients (local (n = 11), hepatic (n = 6) and pulmonary metastases (n = 9)) was compared to conservatively treated patients (local (n = 17), hepatic (n = 37) and pulmonary metastases (n = 8)). RESULTS: Resected PDAC patients suffering from isolated metachronous hepatic metastases initially had a higher T-stage and venous invasion (V1) compared to the other patients. DFS in the metachronous pulmonary metastases group was longer compared to DFS of the hepatic metastases and local recurrence groups. Surgical resection significantly improved PRS in patients with local recurrence and pulmonary metastases, when compared to patients receiving chemotherapy alone. Very-long term survivors (> 5 years) were detected following secondary resection of local recurrence and 45% of these patients were still alive at the end of our study period. CONCLUSION: Although DFS in PDAC patients suffering from isolated local recurrence was dismal and comparable to that of patients with isolated hepatic metastases, very-long term survivors were present only in this group. These results indicate that a surgical approach for isolated local recurrence, if anatomically possible, should be considered.

Chest computed tomography for staging renal tumours: validation and simplification of a risk prediction model from a large contemporary retrospective cohort.

OBJECTIVES: To externally validate a nomogram recently proposed by Larcher et al. (BJU Int. 2017; 120: 490) and to develop a simplified model with comparable accuracy to guide on the need for staging chest computed tomography (CT) for patients with new renal masses. PATIENTS AND METHODS: We analysed the data of 1082 consecutive patients with unilateral enhancing renal masses referred to urology multidisciplinary team meetings at two centres between 2011 and 2017. All patients underwent a staging chest CT at diagnosis. We fitted multivariable logistic regression models and tested the Larcher model performance using area under the receiver-operating curve (AUC), calibration and decision curve analysis. RESULTS: Forty-two patients (3.9%) had a positive chest CT. The Larcher nomogram had an AUC of 83.8% (95% confidence interval [CI] 77.1-90.6), but was only moderately well calibrated (calibration-in-the-large = -0.61, slope = 0.82). Specifically, the nomogram overestimated the risk of positive chest CT, and the magnitude of miscalibration increased with increasing predicted risks. Using a stepwise backward approach, a new model was developed including tumour size, nodal stage and systemic symptoms. Compared with the Larcher model, the new model had a similar AUC (82.7% [95% CI 75.5-90.0]), but improved calibration and clinical net benefit. The predicted risk of positive chest CT was <1% in the low-risk group and 1.9-79.9% in the high-risk group. CONCLUSION: The Larcher nomogram is an accurate prediction tool that was moderately well calibrated with our dataset. However, our simplified model has similar accuracy and uses more objective variables available from referral, so may be easier to incorporate into clinical practice. The low-risk group from our model (tumour size ≤4 cm and no systemic symptoms) had a risk of positive chest CT <1%, suggesting these patients may forego chest CT.