Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.

Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4- CD8- unconventional αß T cells (UTCαß). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTCαß associated with neutrophil-dependent anti-sarcoma immunity. In selected human tumors, including undifferentiated pleomorphic sarcoma, CSF3R expression, a neutrophil signature and neutrophil infiltration were associated with a type 1 immune response and better clinical outcome. Thus, neutrophils driving UTCαß polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Glomus Tumor of the Stomach: A Systematic Review and Illustrative Case Report.

INTRODUCTION: Glomus tumor (GT) is a rare mesenchymal neoplasm that can be found anywhere throughout the body, including the stomach. Our goal was to present a case and a systematic review of the literature, reporting clinical, radiological, surgical, and pathological features of the disease. METHODS: We reviewed Pubmed and SCOPUS for all case reports and case series published after 2000. Papers written in languages different from English and letters to the editor were excluded. Screening and data extraction were performed following the PRISMA guidelines. RESULTS: A total of 89 studies were included in the systematic review, consisting of 187 cases of gastric glomus tumor. Mean age was 52 (18-90); most patients were female (61%). The most common clinical presentation was epigastric pain (33.9% of cases). The gastric antrum was the most frequently involved site (75.3%). Mean tumor size was 2.82 cm (0.8-17). Preoperative diagnosis was achieved in 22 cases, mostly by endoscopic ultrasound (EUS)-guided biopsy. Wedge resection was performed in 62% of treated patients. Smooth muscle actin was expressed in all cases with available immunohistochemistry. Malignant GT was reported in 11 cases. DISCUSSION: Epigastric pain and bleeding were the most common symptoms at presentation in patients with diagnosis of glomus tumor. EUS-guided fine needle aspiration can be useful for preoperative diagnosis. Endoscopic elastosonography is a promising tool for the differential diagnosis of gastric submucosal lesions, including glomus tumors. The treatment of choice is wedge resection with adequate free margins. A laparoscopic approach is warranted when technically feasible. Since malignant gastric GTs have been described, long-term follow-up is suggested after surgical excision.

The Janus-faced role of TRPM2-S in retroperitoneal liposarcoma via increasing ROS levels.

BACKGROUND: Retroperitoneal liposarcoma (RPLS) is a specific soft tissue sarcoma with a high recurrence rate. The short isoform of transient receptor potential cation channel subfamily M member 2 (TRPM2-S) plays an important role in the regulation of reactive oxygen species (ROS). However, the association between TRPM2-S and RPLS and its underlying mechanisms remains unclear. METHODS: The expression of both TRPM2-S and TRPM2-L in RPLS tissues was verified by kimmunohistochemistry (IHC). The regulation on Ca2+ influx by TRPM2-S was evaluated by Fluo-4 AM staining. The effect of TRPM2-S on cell proliferation and apoptosis was tested by 5-Ethynyl-2'-deoxyuridine (EdU) staining and Flow cytometry respectively. The level of cellular ROS was assessed by the DCFH-DA probe. Different concentrations of H2O2 were used to provide oxidative stress on RPLS cells. The underlying mechanisms were further explored by Western blotting. RESULTS: The IHC assays showed that TRPM2-S, but not TRPM2-L, was prognostic in RPLS. Low TRPM2-S level was associated with poor disease-free survival (DFS). Calcium influx signal intensity was significantly decreased under TRPM2-S overexpression, which resulted in a decrease in the levels of FOXO3a and PTEN. Correspondingly, the levels of pERK, pAKT, pP65, pGSK-3ß, Bcl-2, and ß-catenin were upregulated, and cellular ROS was gently increased under TRPM2-S overexpression. Moreover, TRPM2-S slightly promoted cell proliferation and inhibited apoptosis of RPLS cell lines under normoxia, but largely increased apoptosis rates under oxidative stress. The cleaved caspase3 was significantly upregulated by TRPM2-S overexpression under oxidative stress. N-Acetyl-L-cysteine (NAC), a small molecule antioxidant, could largely rescue RPLS cells from the apoptosis induced by H2O2. CONCLUSION: TRPM2-S exerts Janus-faced effects in RPLS by increasing the ROS levels via inhibition on FOXO3a, which promotes cell proliferation under normoxia but induces apoptosis under oxidative stress. Video abstract.

Development of the PERI-Gastric (PEritoneal Recurrence Index) and PERI-Gram (Peritoneal Recurrence Index NomoGRAM) for predicting the risk of metachronous peritoneal carcinomatosis after gastrectomy with curative intent for gastric cancer.

BACKGROUND: A model that quantifies the risk of peritoneal recurrence would be a useful tool for improving decision-making in patients undergoing curative-aim gastrectomy for gastric cancer (GC). METHODS: Five Italian centers participated in this study. Two risk scores were created according to the two most widely used pathologic classifications of GC (the Lauren classification and the presence of signet-ring-cell features). The risk scores (the PERI-Gastric 1 and 2) were based on the results of multivariable logistic regressions and presented as nomograms (the PERI-Gram 1 and 2). Discrimination was assessed with the area under the curve (AUC) of receiver operating curves. Calibration graphs were constructed by plotting the actual versus the predicted rate of peritoneal recurrence. Internal validation was performed with a bootstrap resampling method (1000 iterations). RESULTS: The models were developed based on a population of 645 patients (selected from 1580 patients treated from 1998 to 2018). In the PERI-Gastric 1, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the Lauren diffuse histotype, while in the PERI-Gastric 2, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the presence of signet-ring cells. The AUC was 0,828 (0.778-0.877) for the PERI-Gastric 1 and 0,805 (0.755-0.855) for the PERI-Gastric 2. After bootstrap resampling, the PERI-Gastric 1 had a mean AUC of 0.775 (0.721-0.830) and a 95%CI estimate for the calibration slope of 0.852-1.505 and the PERI-Gastric 2 a mean AUC of 0.749 (0.693-0.805) and a 95%CI estimate for the slope of 0.777-1.351. The models are available at www.perigastric.org . CONCLUSIONS: We developed the PERI-Gastric and the PERI-Gram as instruments to determine the risk of peritoneal recurrence after curative-aim gastrectomy. These models could direct the administration of prophylactic intraperitoneal treatments.

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

Preoperative monocyte-to-lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors.

BACKGROUND AND OBJECTIVES: Several inflammation markers were found to have a prognostic value in cancer. We investigated the significance of preoperative white cell ratios in determining gastrointestinal stromal tumors (GISTs) outcome. METHODS: Clinicopathological features of patients who underwent surgery for GIST were reviewed. The following peripheral blood inflammation markers were calculated: neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-white blood cell ratio (NWR), lymphocyte-white cell ratio (LWR), monocyte-white cell ratio (MWR), and platelet-white cell ratio (PWR). RESULTS: We analyzed 127 patients. Three- and five-year disease-free survival (DFS) were 89.7% and 86.9%, respectively. The univariate analysis selected tumor diameter (P = 0.003), gastric location ( P = 0.024), cell type ( P = 0.024), mitosis ( P < 0.001), MLR ( P = 0.014), NLR ( P = 0.016), and PLR ( P = 0.001) as the factors associated to DFS. The independent prognostic factors for DFS were mitosis ( P = 0.001), NLR ( P = 0.015), MLR ( P = 0.015), and PLR ( P = 0.031), with MLR showing the highest statistical significance and hazard ratio (HR) value. MLR, NLR, and PLR were the only prognostic factors in the subgroup of patients with moderate to high Miettinen's risk class. A high value of MLR was associated with reduced DFS. CONCLUSION: MLR, NLR, and PLR are independent prognostic factors for DFS in GISTs. We first demonstrated the role of MLR as a predictor of recurrence in GIST. Its inclusion into clinical management may improve the recurrence estimation.

Ratio-based staging systems are better than the 7th and 8th editions of the TNM in stratifying the prognosis of gastric cancer patients: A multicenter retrospective study.

BACKGROUND: The current and the previous editions of the tumor-node-metastasis (TNM) system for gastric cancer (GC; TNM8 and TNM7) have a high risk of stage-migration bias when the node count after gastrectomy is suboptimal. Hence, they are possibly not the optimal staging systems for GC patients. This study aims to compare the TNM with two systems less affected by the stage-migration bias, namely, the lymph nodes ratio (LNR) and the log odds of positive lymph nodes (LODDS), to assess which one is the best in stratifying the prognosis of GC patients. METHODS: The sample study included 1221 GC patients. Two 7-cluster staging systems based on the combination of pT categories and LNR and LODDS categories (TLNR and TLODDS) were compared with the two last editions of TNM, using the Akaike information criteria, the Bayesian information criteria, and the receiver operating characteristic (ROC) curve graphs. Further validation on an independent sample of 251 patients was carried out. RESULTS: The univariable and multivariable analyses and the ROC curves detected an advantage of the TLNR and TLODDS systems over the TNM. The TLNR and TLODDS showed the best accuracy both in the subgroup of patients with ≥16 nodes examined. The results were confirmed in the validation analysis. CONCLUSIONS: TLNR and TLODDS staging systems should be considered a valid implementation of the TNM for the prognostic stratification of GC patients. If these results are confirmed in further studies, the future implementation of the TNM should consider the introduction of the LNR or the LODDS along with the number of metastatic nodes.

Prognostic Indicators in Stage IV Surgically Treated Gastric Cancer Patients: A Retrospective Multi-Institutional Study.

INTRODUCTION: The role of gastric resection in treating metastatic gastric adenocarcinoma is controversial. In the present study, we reviewed the short- and long-term outcomes of stage IV patients undergoing surgery. METHODS: A retrospective review was conducted that assessed patients undergoing elective surgery for incurable gastric carcinoma. Short- and long-term results were evaluated. RESULTS: A total of 122 stage IV gastric cancer patients were assessed. Postoperative mortality was 5.7%, and the overall rate of complications was 35.2%. The overall survival rate at 1 and 3 years was 58 and 19% respectively; the median survival was 14 months. Improved survival was observed for the factors age less than 60 years (p = 0.015), site of metastases (p = 0.022), extended lymph node dissection (p = 0.044), absence of residual disease after surgery (p = 0.001), and administration of adjuvant chemotherapy (p = 0.016). Multivariate analysis showed that residual disease and adjuvant chemotherapy were independent prognostic factors. CONCLUSIONS: The results of this study suggest that surgery combined with systemic chemotherapy in selected patients with stage IV gastric cancer can improve survival.

Role of surgery in the multimodal treatment of primary and recurrent leiomyosarcoma of the inferior vena cava.

BACKGROUND: The optimal treatment of leiomyosarcoma (LMS) of the inferior vena cava (IVC) is still unclear, especially in the metastatic and/or recurrent setting. We herein evaluated the long-term outcome after aggressive management. METHODS: Eleven patients underwent surgery for primary LMS of the IVC between 2000 and 2012. The clinical, pathological, and survival data were reviewed. RESULTS: The IVC was managed by graft replacement in four cases, primary repair in four, and ligation in three. The R0 resection rate was 64%. The median follow-up was 60 months. Nine patients developed distant relapse, two of them concomitant local recurrence; no exclusive local recurrence was observed. The 3- and 5-year distant recurrence free survival were 30% and 10%, respectively. The 3- and 5-year overall-survival (OS) were 77.8%. The presence of residual disease after surgery (P = 0.024) and the time to recurrence (P = 0.033) were associated with the OS in a univariate analysis. The time to recurrence was related to the post-metastases survival (P = 0.032). CONCLUSIONS: An adequate surgery minimizes the risk of local recurrence and remains the main treatment for primary LMS of the IVC. Nevertheless, the rate of distant metastases remains extremely high. An aggressive surgical policy may be of benefit to selected patients with metastatic disease. J. Surg. Oncol. 2016;114:44-49. © 2016 Wiley Periodicals, Inc.

Surgical management of intraabdominal metastases from melanoma: role of the neutrophil to lymphocyte ratio as a potential prognostic factor.

BACKGROUND: The aims of this study were to evaluate the role of surgery in the management of patients with intraabdominal metastases from melanoma and to investigate the neutrophil to lymphocyte ratio (NLR) as prognostic factor in this group of patients. METHODS: Altogether, 44 patients who underwent surgery for Intraabdominal metastases from melanoma with curative, cytoreductive, or palliative intent were analyzed. RESULTS: There were 77 intraabdominal organ resections performed during the 44 operations. R0 resection was achieved in 19 (43 %) cases. Factors associated with R0 resection were an absence of extra-abdominal metastases, low serum lactate dehydrogenase, involvement of fewer than three sites, and the presence of fewer than three metastatic lesions. The 1-, 3-, and 5-year overall survival rates were, respectively, 79, 66, and 44 % in the curative intent group; 36, 18, and 9 % in the cytoreduction group; and 21, 0 and 0 % in the palliation group (curative intent vs. cytoreduction vs. palliation p < 0.001). By Cox's multivariate analysis, the independent prognostic factors were time from excision of primary melanoma to the diagnosis of intraabdominal metastases, NLR, and residual disease after surgery. CONCLUSIONS: Our results confirm the usefulness of major surgical interventions as reported in previous studies. We reviewed recent evidence that immunologic phenomena may explain the unexpectedly good response rate in patients with advanced disease. The simple estimation of the NLR has been advocated as a prognostic marker for several cancers. We show that it is likewise useful in metastatic melanoma. We stress the need for developing additional immunologic markers.

Prognostic factors for primary gastrointestinal stromal tumours: are they the same in the multidisciplinary treatment era?

PURPOSE: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumour of the gastrointestinal tract. The introduction of tyrosine kinase inhibitors (TKIs) has lead to increasing use of combination of medical and surgical therapy. The aim of this study was to look at outcomes from a series of surgically treated GISTs and determine prognostic factors in the context of multimodal therapy. METHODS: We analysed 104 single surgeon's patients with GIST. End points of the study were disease-specific survival (DSS), disease-free survival (DFS) and post-operative complications. RESULTS: Three- and 5-year DSS rates were 96.7 and 94.6 %. On univariate analysis, clear resection margins were predictive of DSS. Patients with R2 resection had a worse prognosis (3-year DSS rate of 83.3 %; 5-year DSS rate of 62.5 %) compared to patients with R0 (3-year DSS rate of 98 %; 5-year DSS rate of 98 %) or R1 resection (3-year DSS rate of 100 %; 5-year DSS rate of 100 %) (R0 vs R1 vs. R2 p = 0.001). Pre-operative factors associated with R2 resection were clinical metastatic disease (p < 0.001), non-gastric tumour site (p = 0.002) and large tumour diameter (p = 0.031). Three- and 5-year DFS rates were 65.5 and 59.8 %. Serosal perforation (p = 0.013) and mitotic rate (p = 0.05) were found to be independently predictive of increased DFS. The presence of serosal perforation was associated with tumour site (p = 0.018), mitotic rate (p = 0.035), tumour diameter (p < 0.001), growth pattern (p = 0.007) and age (p = 0.040). CONCLUSIONS: In the multidisciplinary management of GIST, serosal perforation may represent an additional predictor of recurrence along with mitotic rate. Complete macroscopic surgical resection is the most reliable prognostic factor, and an aggressive surgical approach should be advocated.

Combined ultrasonic aspiration and saline-linked radiofrequency precoagulation: a step toward bloodless liver resection without the need of liver inflow occlusion: analysis of 313 consecutive patients.

BACKGROUND: Hemorrhage is undoubtedly one of the main factors contributing to morbidity and mortality in liver resections. Vascular occlusion techniques are effective in controlling intraoperative bleeding, but they cause liver damage due to ischemia. We evaluated the effectiveness and safety of using a combined technique for hepatic parenchymal transection without liver inflow occlusion. METHODS: Three hundred and thirteen consecutive patients who underwent liver resection in four hepato-pancreato-biliary units. Hepatic parenchymal transection was carried out using a combined technique of saline-linked radiofrequency precoagulation and ultrasonic aspiration without liver inflow occlusion. RESULTS: During the study period 114 minor and 199 major hepatic resections were performed. The mean amount of intraoperative blood loss was 377 ml (SD 335 ml, range 50 to 2,400 ml) and the blood transfusion rate was 10.5%. The median amount of blood loss during parenchymal transection and parenchymal transection time was 222 ml (SD 224 ml, range 40 to 2,100 ml) and 61 minutes (range 12 to 150 minutes) respectively. There were two postoperative deaths (0.6%). Complications occurred in 84 patients (26.8%) and most complications were minor. CONCLUSIONS: Combined technique of saline-linked radiofrequency ablation and ultrasonic aspiration for liver resection is a safe method for both major and minor liver resections. The method is associated with decreased blood loss, reduced postoperative morbidity, and minimal mortality rates. We believe that this combined technique is comparable to other techniques and should be considered as an alternative.

Prognostic value of mitotic count in leiomyosarcoma: A comprehensive monocentric retrospective study.

BACKGROUND: Leiomyosarcomas (LMSs) include heterogeneous entities with different clinical courses not entirely predicted by known prognostic factors. In particular, the value of mitotic count as independent prognostic factor in LMS has been poorly investigated. METHODS: We retrospectively analyzed all patients with a diagnosis of LMS who accessed to our Institution from June 1999 to May 2022 for which mitotic count was numerically expressed within the pathology report. Univariate and multivariate analyses were conducted to explore the prognostic value of mitotic count along with other clinical and histological variables. RESULTS: We identified 121 eligible patients, with a median follow-up of 91.03 months (range 0.62-275.2 months). Median progression-free survival (mPFS) was 16.7 months, and median overall survival (mOS) was 105.6 months. In univariate analysis, mitotic count showed a significant impact on PFS and OS, with an hazard ratio per mitotic unit of 1.03 (1.01-1.04, p < 0.001) and 1.03 (1.01-1.04, p = 0.007), respectively. Similar results were found for locally advanced and metastatic patients, separately. Other significant prognostic factors for PFS were stage at diagnosis, performance status, tumor size and Ki-67, while differentiation, necrosis, grade, stage at diagnosis, tumor size, performance status and age at diagnosis were identified for OS. In multivariate analysis, the only significant factors were mitotic count and the presence of metastases at diagnosis for PFS, whereas the same two factors plus age at diagnosis were identified for OS. CONCLUSION: Mitotic count represented the most important histological prognostic factor for OS and PFS in localized and metastatic LMS.

Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

"Chronic" metastatic pancreatic acinar cell carcinoma.

Acinar cell carcinoma (ACC) of the pancreas is a rare exocrine tumour for which there is very limited information about chemotherapy regimens and prognosis. Even though there are clinical guidelines for management of ductal cell carcinoma, a definitive and specific regime has not yet been agreed for this type of pancreatic cancer. We report a case of metastatic ACC of pancreas who has been treated with a multimodal approach, including novel combinations of different targeted drugs with conventional chemotherapy, surgery and radiofrequency ablation since the last 11 years. This degree of long term survival has not been reported so far in such a case of metastatic ACC of the pancreas. This case highlights the importance of a personalised multidisciplinary therapeutic strategy, employing locoregional therapies along with combinations of established and novel systemic therapies to control the disease, and the importance of flexibility when instigating new treatment paradigms for progressive cancer. Also, this case demonstrates that complete tumour eradication may not be the sole purpose of surgical oncology.